Membrane Proteins: Targeting, Structure, Function, and Regulation
Na,K-ATPase, Ca-ATPase, and Lysosome-Associated Membrane Proteins (LAMPs)

To identify the pathway and mechanisms by which lysosomal membrane proteins are delivered after biosynthesis to the lysosomal membrane, portions of the encoding DNA for these lysosomal proteins were spliced together with encoding DNA for a plasma membrane protein to generate genes that encode chimeric proteins. When these were expressed in tissue cultured cells, a short region at the C-terminal end of the lysosomal proteins was necessary and sufficient to target chimeric proteins to the lysosome. LEP 100 (also known as LAMP-1) and LAMP-2 have recently been implicated in cell movements during development and in metastasis of cancer cells. In this latter role these proteins appear at the cell surface. We are currently exploring the cellular mechanisms that regulate the distribution of the proteins between lysosomes and the plasma membrane.

The figure shows immunofluorescence micrographs of the cellular distribution of a chimera that includes the C-terminal cytoplasmic tail of LAMP-1 (left) and the reverse chimera that has the VSV-G protein cytoplasmic tail (right). Targeting is to lysosomes (left) and the plasma membrane (right) in mouse-L cells.

LAMP-1 is expressed from a single sized transcript and appears to be a housekeeping protein. LAMP-2 is expressed as three splice variants. RNA splicing results in the production of three isoforms of LAMP-2 that differ in their targeting sequences. When expressed in tissue cultured mammalian cells, the three isoforms show differences in subcellular distribution. LAMP-2c targets largely to lysosomes, whereas LAMP-2a and to an even greater extent LAMP-2b have a substantial presence at the plasma membrane at steady state. These aspects of LAMP behavior are consistent with the LAMP-2 molecules, at least, playing a biological role at the plasma membrane as well as in lysosomes.

In order to determine the normal biological functions of the LAMPs, we are taking several approaches. First, we have identified a possible homologue in C. elegans. We are studying its cellular and subcellular distribution and recently obtained a null mutation that appears to have altered gut morphology. Second, we are making transgenic mice that express mis-targeted versions of LAMP proteins. Third, we are producing gene knock-outs of the two known mouse LAMP genes.

Ion transport by the sarcoplasmic reticulum Ca-ATPase in the heart is modulated by a small protein, phospholamban, allowing heart beat rate to increase in response to adrenalin. We are making mutations in these proteins to determine what aspects of their structures are critical for localization in the sarcoplasmic reticulum and what aspects are involved in their interaction. The Ca-ATPase is homologous in structure to the Na,K-ATPase, yet they reside in different cell membranes and transport different cations. By studying the properties of chimeric proteins that contain portions of each, we are exploring what aspects of structure are involved in ion selectivity and what aspects are involved in differential localization in the cell.

The Na/K-ATPase (sodium pump) plays a key role in regulation of ion balance, and thus is directly involved in regulation of cardiac function, blood pressure, and nerve and muscle excitability. The sodium pump consists of two subunits. We are studying the sites of interaction between the alpha and ß-subunits and the cellular mechanisms involved in regulation of subunit biosynthesis and assembly. In typical polarized epithelia, the sodium pumps occur only in the basolateral membrane, where they participate in vectorial transport of ions. There is some evidence that this localization may be perturbed in polycystic kidney disease. We are studying the mechanisms governing selective localization of sodium pumps in the plasma membrane. In Drosophila there is a single gene for the catalytic a-subunit of the sodium pump. Recently we characterized several mutations in this gene, including one which is a cold-sensitive lethal. This mutations are expecially interesting because it shifts the temperature tolerance range as well as causing a variety of behavioral changes.

Immunofluorescence micrograph showing the distribution of the sodium pump alpha subunit in the whole adult fly. The top of the montage is dorsal, left is anterior. dvm = indirect flight muscle; e = eye; b = brain; pr = proboscis and mouth parts; le = leg muscle; a = abdomen; m = malpighian tubules; tn = thoracic neuromere. From Lebovitz et al. (1989).

The sodium pump and the calcium pump are members of a large family of ATPases that include examples from every phylum. We have begun investigations of the phylogenetic relationships among these ATPases, using PCR based cloning of representatives from key taxomonic groups and sequence analysis programs to evaluate evolutionary relatedness.

Selected Recent Publications

Na,K- and Ca-ATPases

1. Campbell, A.M., Kessler, P.D. and Fambrough, D.M. 1992. The alternate carboxyl termini of avian cardiac and brain SR/ER Ca-ATPases are on opposite sides of the membrane. J. Biol. Chem. 267, 9321-9325.
2. Hamrick, M., K. J. Renaud and D. M. Fambrough. 1993. Assembly of the extracellular domain of the Na,K-ATPase b subunit with the a subunit. Analysis of b subunit chimeras and carboxyl-terminal deletions. J. Biol. Chem., 268: 24367-24373.
3. Campbell, A. M., F. Wuytack and D. M. Fambrough. 1993. Differential distribution of the alternative forms of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, SERCA2b and SERCA2a, in the avian brain. Brain Res. 605: 67-76.
4. Takeyasu, K., M. Hamrick, A. M. Barnstein, and D. M. Fambrough. 1993. Structural analysis and expression of a chromosomal gene encoding an avian (Na+ + K+)- ATPase b1-subunit. Biochim. Biophys. Acta. 1172: 212-216.
5. Lemas, M. V. and D. M. Fambrough. 1993. Sequence analysis of DNA encoding an avian Na+,K+-ATPase b2-subunit. Biochim. Biophys. Acta 1149: 339-342.
6. Geering, K., P. Jaunin, F. Jaisser, A. M. Merillat, J. D. Horisberger, P. M. Mathews, V. Lemas, D. M. Fambrough and B. C. Rossier. 1993. Mutation of a conserved proline residue in the b-subunit ectodomain prevents Na,K-ATPase oligomerization. Am. J. Physiol., 265: C1169-C1174.
7. Sumbilla, C., L. Lu, D. Lewis, G. Inesi, T. Ishii, K. Takeyasu, Y. Feng and D. M. Fambrough. 1993. Ca2+ dependence and thapsigargin inhibited phosphorylation of Na,K-ATPase catalytic domain following chimeric recombination with the Ca2+-ATPase. J. Biol. Chem., 268: 21185- 21190.
8. Emerick, M.C. and Fambrough, D. M. 1993. Intramolecular fusion of Na pump subunits assures exclusive assembly of the fused a and b subunit domains into a functional enzyme in cells also expressing endogenous Na pump subunits. J. Biol. Chem. 268, 23455-23459.
9. Lemas, M. V., Hamrick, M., Takeyasu, K and Fambrough, D. M. 1994. 26 Amnino acids of an extracellular domain of the Na,K-ATPase a-subunit are sufficient for assembly with the Na,K-ATPase b-subunit. J. Biol. Chem. 269, 8255-8259.
10. Song, Y. and D. M. Fambrough. 1994. Molecular evolution of the calcium-transporting ATPases analyzed by the maximum parsimony method. In "Molecular Evolution of Physiological Processes" (D. M. Fambrough, ed.) Rockefeller University Press, N.Y., pp. 271-283.
11. Lemas, M. V., H.-Y. Lu, K. Takeyasu, B. Kone and D. M. Fambrough. 1994. Assembly of the Na,K-ATPase a-subunit isoforms with the Na,K- and H,K-ATPase b-subunit isoforms. J. Biol. Chem., 269: 18651-18655.
12. Fambrough, D.M., Lemas, M.V., Hamrick, M., Emerick, M., Renaud, K.J., & Inman, E.M., Hwang, B. and Takeyasu, K. 1994. Analysis of subunit assembly of the Na-K-ATPase. Am. J. Physiol. 266, C579-C589.
13. Schubiger, M., Feng, Y., Fambrough, D. M. and Palka, J.1994. A mutation of the Drosophila sodium pump a-subunit gene results in bang-sensitive paralysis. Neuron 12, 373-381.
14. Davis, M.W., Somerville, D., Lee, R.Y.N., Lockery, S., Avery, L. and Fambrough, D.M. 1995. Mutations in the Caenorhabditis elegans Na,K-ATPase a-subunit gene, eat-6, disrupt excitable cell function. J. Neuroscience 15, 8408-8418.
15. Fambrough, D.M. and G. Inesi. 1996. Cation Transport ATPases. In "Molecular Biology of Membrane Disorders" (S. Schultz et al., Editors) Plenum Press. pp 223-241.
16. Yu, H.-Y., S. Nettikadan, D.M. Fambrough and K. Takeyasu. 1996. Negative transcriptional regulation of the chicken Na+/K+-ATPase a1 subunit gene. Biochim. Biophys. Acta 1309: 239-252.
17. Kaprielian, Z., S. W. Robinson, D.M. Fambrough and P.D. Kessler. 1996. Movement of Ca2+-ATPase molecules within the sarcoplasmic/endoplasmic reticulum in skeletal muscle. J. Cell Sci. 109: 2529-2537.
18. Ishii, T., F. Hata, M.V. Lemas, D.M. Fambrough and K. Takeyasu. 1997. Carboxy-terminal regions of the SERCA- and Na+/K+-ATPases control their K+-selectivity. Biochemistry 36: 442-451.
19. Colonna, T., M. Kostich, M. Hamrick, B. Hwang, J.D. Rawn and D. M. Fambrough 1997. Subunit Interactions in the Sodium Pump. Ann. N.Y. Acad. Sci. 834: 498-513.
20. Colonna, T. L. Huynh, and D. M. Fambrough. 1997. Subunit interactions in the Na,K-ATPase explored with the yeast two-hybrid system. J. Biol. Chem. 272: 12366-12372
21. Feng, Y., L. Huynh, K. Takeyasu, and D. M. Fambrough. 1997. The Drosophila Na, K-ATPase a-subunit gene: gene structure, promoter function, and analysis of a cold-sensitive recessive lethal mutation. Genes and Function 1: 91-116.
22. Zhou, X. and D. M. Fambrough. 1999. Expression of the avian Na,K-ATPase subunits in Dictyostelium discoideum. J. Membrane Biol 167: 19-24.
23. Wilson, P.D., Devuyst, O., Gatti, L., Falkenstein, D., Robinson, S. and D. M. Fambrough. 2000. Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidneydisease epithelia is associated with aberrant expressionof the beta-2 isoform. Am. J. Pathol. 156: 1-16.
24. Fambrough, D., Huynh, H.L. and Hwang, B. 2000. The Na,K-ATPase alpha-beta subunit assembly site. In Na/K-ATPase and Related ATPases. 9th International Conference on Na/K Pump and Related Pumps (K. Taniguchi and S. Kaya, eds.) Elsevier, Amsterdam, pp 103-106.
25. Okamura, H., Yasuhara, J.C., Fambrough, D.M., and Takeyasu, K. 2003. P-type ATPases in Caenorhabditis and Drosophila: Implications for evolution of the P-type ATPase subunit families with special reference to the Na,K-ATPase and H,K-ATPase subgroup. J. Memb. Biol. 191 (in press for Jan issue)

Lysosome-Associated Membrane Proteins

1. Mathews, P. M., J. B. Martinie, and D. M. Fambrough. 1992. The pathway and targeting signal for delivery of the integral membrane glycoprotein LEP100 to lysosomes. J. Cell Biol., 118: 1027-1040.
2. Hatem, C.L., Gough, N.R. and Fambrough, D.M. 1995. Multiple mRNAs encode the avian lysosomal membrane protein LAMP-2, resulting in alternative transmembrane and cytoplasmic domains. J. Cell Sci. 108, 2093-2100.
3. Gough, N.R., C. L. Hatem, and D.M. Fambrough. 1995. The family of LAMP-2 proteins arise by alternative splicing from a single gene. Characterization of the avian LAMP-2 gene and identification of mammalian homologs of LAMP-2b and LAMP-2c. DNA and Cell Biology. 14: 863-867.
4. Gough, N.R. and D.M. Fambrough. 1997. The different cytoplasmic domains of avian LAMP-2a,b and c confer different cellular distributions to chimeric LAMP-1/LAMP-2 proteins. J. Cell Biol. 137: 1161-1169.
5. Gough, N.R., M.E. Zweifel, O. Martinez-Augustin, R.C. Aguilar, J.S. Bonifacino and D.M. Fambrough. 1999. Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXX[hydrophobe] targeting signals. J. Cell Sci.: 4257-4269.
6. Kostich, M., Fire, A. and Fambrough, D.M. 2000. Identification and molecular-genetic characterization of a LAMP/CD68-like protein from Caenorhabditis elegans. J. Cell Biol. 113: 2595-2606.

Major Earlier Publications

HISTONES:

1. Fambrough, D. M. and J. Bonner. 1966. On similarity of plant and animal histones. Biochemistry 5: 2563-2570.
2. Fambrough, D. M. and J. Bonner. 1968. Sequence homology and role of cysteine in plant and animal arginine-rich histones. J. Biol. Chem. 243: 4434-4439.
3. DeLange, R. J., D. M. Fambrough, E. Smith and J. Bonner. 1968. Calf and pea histone IV. I. Amino acid compositions and the identical COOH-terminal 19-residue sequence. J. Biol. Chem. 243: 5906-5913.
4. Bonner, J., M. E. Dahmus, D. M. Fambrough, R. C. Huang, K. Marushige and D. Y. Tuan. 1968. The biology of isolated chromatin. Science 159: 47-53.
5. DeLange, R., J., D. M. Fambrough, E. Smith and J. Bonner. 1969. Calf and pea histone IV. II. The complete amino acid sequence of calf thymus histone IV; presence of epsilon-N-acetyllysine. J. Biol. Chem. 244: 319-334.
6. DeLange, R. J., D. M. Fambrough, E. Smith and J. Bonner. 1969. Calf and pea histone IV. III. Complete amino acid sequence of pea seedling histone IV; comparison with the homologous calf thymus histone. J. Biol. Chem. 244: 5669- 5679.

ACETYLCHOLINE RECEPTORS AND NEUROMUSCULAR JUNCTIONS:

1. Fambrough, D. M. 1970. Acetylcholine sensitivity of muscle fiber membranes: mechanism of regulation by motoneurons. 1970. Science 168: 372-373.
2. Fambrough, D. M. and J. E. Rash. 1971. Development of acetylcholine sensitivity during myogenesis. Devel. Biol. 26: 55-68.
3. Fambrough, D. M. and H. C. Hartzell. 1972. Acetylcholine receptors: number and distribution at neuromuscular junctions in rat diaphragm. Science 176: 189-191.
4. Hartzell, H. C. and D. M. Fambrough. 1972. Acetylcholine receptors: distribution and extrajunctional density in rat diaphragm after denervation correlated with acetylcholine sensitivity. J. Gen. Physiol. 60: 248-262.
5. Hartzell, H. C. and D. M. Fambrough. 1972. Acetylcholine receptors production and incorporation into membranes of developing muscle fibers. Devel. Biol. 30: 153-165.
6. Fambrough, D. M., D. B. Drachman and S. Satyamurti. 1973. Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science 182: 293-295.
7. Devreotes, P. N. and D. M. Fambrough. 1975. Acetylcholine receptor turnover in membranes of developing muscle fibers. J. Cell Biol. 65: 335-358.
8. Ritchie, A. K. and D. M. Fambrough. 1975. Ionic properties of the acetylcholine receptor in cultured rat myotubes. J. Gen. Physiol. 65: 751-767.
9. Ritchie, A. K. and D. M. Fambrough. 1975. Electrophysiological properties of the membrane and acetylcholine receptor in developing rat and chick myotubes. J. Gen. Physiol. 66: 327-355.
10. Devreotes, P. N. and D. M. Fambrough. 1976. Synthesis of acetylcholine receptors by cultured chick myotubes and denervated mouse extensor digitorum longus muscles. Proc. Natl. Acad. Sci. U.S.A. 73: 161-164.
11. Devreotes, P. N. and D. M. Fambrough. 1976. Turnover of acetylcholine receptors in skeletal muscle. Cold Spring Harbor Symp. Quant. Biol. 40: 237-251.
12. Devreotes, P. N., J. M. Gardner and D. M. Fambrough. 1977. Kinetics of biosynthesis of acetylcholine receptor and subsequent incorporation into plasma membrane of cultured chick skeletal muscle. Cell. 10: 365-373.
13. Fambrough, D. M. and P. N. Devreotes. 1978. Newly synthesized acetylcholine receptors are located in the Golgi apparatus. J. Cell Biol. 76: 237-244.
14. Carbonetto, S. T., D. M. Fambrough and K. J. Muller. 1978. Nonequivalence of a- bungarotoxin receptors and acetyolcholine receptors in chick sympathetic neurons. Proc. Natl. Acad. Sci. U.S.A. 75: 1016-1020.
15. Gardner, J. M. and D. M. Fambrough. 1979. Acetylcholine receptor degradation measured by density labeling: effect of cholinergic ligands and evidence against recycling. Cell 16: 661-674.
16. Linden, D. C. and D. M. Fambrough. 1979. Biosynthesis and degradation of acetylcholine receptors in rat skeletal muscle. Effects of electrical stimulation. Neuroscience 4: 527-538.
17. Carbonetto, S. T. and D. M. Fambrough. 1979. Synthesis, insertion into the plasma membrane and turnover of a-bungarotoxin receptors in chick sympathetic neurons. J. Cell Biol. 81: 555-569.
18. Fambrough, D. M. 1979. Control of acetylcholine receptors in skeletal muscle. Physiol. Rev. 59: 165-227.
19. Pumplin, D. W. and D. M. Fambrough. 1982. Turnover of acetylcholine receptors in skeletal muscle. Ann. Rev. Physiol. 44: 319-335.
20. Anderson, M. J. and D. M. Fambrough. 1983. Aggregates of acetylcholine receptors are associated with plaques of a basal lamina heparan sulfate proteoglycan on the surface of skeletal muscle fibers. J. Cell Biol. 97: 1396-1411.

ACETYLCHOLINESTERASE

1. Rotundo, R. L. and D. M. Fambrough. 1979. Molecular forms of chicken embryo acetylcholinesterase in vitro and in vivo: isolation and characterization. J. Biol. Chem. 254: 4790-4799.
2. Rotundo, R. L. and D. M. Fambrough. 1980. Synthesis, transport and fate of acetylcholinesterase in cultured chick embryo muscle cells. Cell 22: 583-594.
3. Rotundo, R. L. and D. M. Fambrough. 1980. Secretion of acetylcholinesterase; relation to acetylcholine receptor metabolism. Cell 22: 595-602.
4. Fambrough, D. M., A. G. Engel and T. L. Rosenberry. 1982. Acetylcholinesterase of human erythrocytes and neuromuscular junctions: homologies revealed by monoclonal antibodies. Proc. Natl. Acad. Sci. U.S.A. 79: 1078-1082.
5. Hedreen, J. C., G. R. Uhl, S. J. Bacon, D. M. Fambrough and D. L. Price. 1984. Acetylcholinesterase immunoreactive axonal network in monkey visual cortex. J. Comp. Neurol. 226: 246 254.
6. Rotundo, R. L. and D. M. Fambrough. 1986. Function and molecular structure of acetylcholinesterase. In Myology (A. G. Engel and B. Q. Banker, eds.) McGraw Hill Book Co., New York. pp. 791-810.

EXTRACELLULAR MATRIX

1. Chiquet, M. and D. M. Fambrough. 1983. Cellular origin of extracellular matrix components during muscle morphogenesis revealed by monoclonal antibodies. In Limb Development and Regeneration, Alan R. Liss, New York, pp. 359-368.
2. Gardner, J. M. and D. M. Fambrough. 1983. Fibronectin expression during myogenesis. J. Cell Biol. 96: 474-485.
3. Chiquet, M. and D. M. Fambrough. 1984. Chick myotendinous antigen: I. A monoclonal antibody as a marker for tendon and muscle morphogenesis. J. Cell Biol. 98: 1926-1936.

(Note: Myotendinous antigen was later renamed "tenescin" by Matthias Chiquet and Ruth Ehrismann-Chiquet)

4. Chiquet, M. and D. M. Fambrough. 1984. Chick myotendinous antigen: II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits. J. Cell Biol. 98: 1937-1946.
5. Bayne, E. K., M. J. Anderson and D. M. Fambrough. 1984. Extracellular matrix organization in developing muscle: Correlation with acetylcholine receptor aggregates. J. Cell Biol. 99: 1486-1501.

MISCELLANEOUS MEMBRANE STUDIES

1. Rash, J. E. and D. M. Fambrough. 1973. Ultrastructural and electrophysiological correlates of cell coupling and cytoplasmic fusion during myogenesis in vitro. Devel. Biol. 30: 166-186.
2. Edidin, M. and D. Fambrough. 1973. Fluidity of the surface of cultured muscle fibers: rapid lateral diffusion of marked surface antigens. J. Cell Biol. 57: 27-37.
3. Powell, J. A. and D. M. Fambrough. 1973. Electrical properties of normal and dysgenic mouse skeletal muscle in culture. J. Cell. Physiol. 82: 21-38.
4. Kehry, M., S. Ewald, R. Douglas, C. Sibley, W. Raschke, D. Fambrough, and L. Hood. 1980. The immunoglobulin chains of membrane-bound and secreted IgM molecules differ in their C-terminal segments. Cell 21: 393-406.
5. Wakshull, E., E. K. Bayne, M. Chiquet and D. M. Fambrough. 1983. Characterization of a plasma membrane glycoprotein common to myoblasts, skeletal muscle satellite cells and glia. Devel. Biol. 100: 464-477.
6. Hille, B. and D. M. Fambrough (Editors). 1987. "Proteins of Excitable Membranes," 331 pp., Wiley-Interscience, New York.

LYSOSOME-ASSOCIATED MEMBRANE PROTEINS

1. Lippincott-Schwartz, J. and D. M. Fambrough. 1986. Lysosomal membrane dynamics: Structure and inter-organellar movement of a lysosomal membrane glycoprotein. J. Cell Biol. 102: 1593-1605.
2. Lippincott-Schwartz, J. and D. M. Fambrough. 1987. Cycling of the integral membrane glycoprotein, LEP100, between plasma membrane and lysosomes: Kinetic and morphological analysis. Cell, 49: 669-677.
3. Mathews, P. and D. M. Fambrough. 1988. Structure-behavior correlates for the shuttling membrane glycoprotein LEP100. J. Gen. Physiol. 92: 18a.
4. Fambrough, D. M., K. Takeyasu, J. Lippincott-Schwartz, and N. R. Siegel. 1988. Structure of LEP100, a glycoprotein that shuttles between lysosomes and the plasma membrane, deduced from the nucleotide sequence of the encoding cDNA. J. Cell Biol. 106: 61-67.
5. Zot, A. S. and D. M. Fambrough. 1990. Structure of a gene for a lysosomal membrane glycoprotein (LEP100): housekeeping gene with unexpected exon organization. J. Biol. Chem. 265: 20988-20995.
6. Nabi, I. R., A. Le Bivic, D. Fambrough, and E. Rodriguez-Boulan. 1991. An endogenous MDCK lysosomal membrane glycoprotein is targeted basolaterally before delivery to lysosomes. J. Cell Biol., 115: 1573-1584.

P-TYPE ATPases

1. Fambrough, D. M. and E. K. Bayne. 1983. Multiple forms of (Na+ + K+)-ATPase in the chicken: selective detection of the major nerve, skeletal muscle, and kidney form by a monoclonal antibody. J. Biol. Chem. 258: 3926-3935.
2. Pumplin, D. W. and D. M. Fambrough. 1983. (Na+ + K+)-ATPase correlated with a major group of intramembranous particles in freeze fracture replicas of cultured chick myotubes. J. Cell Biol. 97: 1214-1225.
3. Fambrough, D. M. 1983. Studies on the (Na+ + K+)-ATPase of skeletal muscle and nerve. Cold Spring Harbor Symp. Quant. Biol. 48: 297-304.
4. Tamkun, M. M. and D. M. Fambrough. 1986. The (Na+ + K+)-ATPase of chick sensory neurons: Studies on biosynthesis and intracellular transport. J. Biol. Chem. 261: 1009-1019.
5. Wolitzky, B. A. and D. M. Fambrough. 1986. Regulation of the (Na+ + K+)-ATPase in cultured chick skeletal muscle: Modulation of expression by demand for ion transport. J. Biol. Chem. 261: 9990-9999.
6. Fambrough, D. M., B. A. Wolitzky, M. M. Tamkun and K. Takeyasu. 1987. Regulation of the sodium pump in excitable cells. Kidney International 32: S97-S112.
7. Takeyasu, K., M. M. Tamkun, N. R. Siegel and D. M. Fambrough. 1987. Expression of hybrid (Na+ + K+)-ATPase molecules after transfection of mouse Ltk- cells with DNA encoding the b-subunit of an avian brain sodium pump. J. Biol. Chem. 262: 10733-10740.
8. Kaprielian, Z. and D. M. Fambrough. 1987. Expression of fast and slow isoforms of the Ca2+-ATPase in developing chick skeletal muscle. Devel. Biol. 124: 490 503.
9. Takeyasu, K., M. M. Tamkun, K. Renaud, and D. M. Fambrough. 1988. Ouabain- sensitive (Na+ + K+)-ATPase activity expressed in mouse Ltk- cells by transfection with DNA encoding the alpha-subunit of an avian sodium pump. J. Biol. Chem. 263: 4347-4354.
10. Fambrough, D. M. 1988. The sodium pump becomes a family. Trends in Neuroscience 11: 325-328.
11. Takeyasu, K., K. J. Renaud, J. P. Taormino, B. A. Wolitzky, A. Barnstein, M. M. Tamkun, and D. M. Fambrough. 1989. Differential subunit and isoform expression are involved in regulation of the sodium pump in skeletal muscle. Curr. Topics in Memb. Transport 34: 143-165.
12. Lebovitz, R. M., K. Takeyasu, and D. M. Fambrough. 1989. Molecular characterization and expression of the (Na+ + K+)-ATPase a-subunit in Drosophila melanogaster. EMBO J. 8: 193-202.
13. Karin, N. J., Z. Kaprielian, and D. M. Fambrough. 1989. Expression of avian Ca2+- ATPase cDNA in cultured mouse myogenic cells. Mol. Cell. Biol. 9: 1978-1986. Kaprielian, Z., A. M. Campbell, and D. M. Fambrough. 1989. Identification of a Ca2+- ATPase in cerebellar Purkinje cells. Mol. Brain Res. 6: 55-60.
14. Taormino, J. P. and D. M. Fambrough. 1990. Pre-translational regulation of the (Na+ + K+)-ATPase in response to demand for ion transport in cultured chicken skeletal muscle. J. Biol. Chem. 265: 4116-4123.
15. Takeyasu, K., V. Lemas and D. M. Fambrough. 1990. Stability of (Na+ + K+)-ATPase alpha-subunit isoforms in evolution. Amer. J. Physiol. 259: C619-630.
16. Kaprielian, Z., E. Bandman, and D. M. Fambrough. 1991. Expression of Ca2+-ATPase isoforms in denervated, regenerating, and dystrophic chicken skeletal muscle. Devel. Biol., 144: 199-211.
17. Campbell, A. M., P. D. Kessler, Y. Sagara, G. Inesi, and D. M. Fambrough. 1991. Nucleotide sequences of avian cardiac and brain SR/ER Ca2+-ATPases and functional comparisons with fast twitch Ca2+-ATPase: calcium affinities and inhibitor effects. J. Biol. Chem. 266: 16050-16055.
18. Renaud, K. J., E. M. Inman and D. M. Fambrough. 1991. Cytoplasmic and transmembrane domain deletions of Na,K-ATPase b-subunit: effects on subunit assembly and intra- cellular transport. J. Biol. Chem., 266: 20491-20497.
19. Luckie, D. B., V. Lemas, K. L. Boyd, D. M. Fambrough, and K. Takeyasu. 1992. Molecular dissection of functional domains of the E1E2-ATPase using sodium and calcium pump chimeric molecules. Biophysical J. 62: 220-227.
20. Lemas, M. V., K. Takeyasu and D. M. Fambrough. 1992. The carboxyl terminal 161 amino acids of the Na,K-ATPase a-subunit are sufficient for assembly to the b-subunit. J. Biol. Chem., 267: 20987-20991.

• Born: July 22, 1941 - Durham, North Carolina
• Married: June 1963 - to Zarelda Walston
• Children: Benjamin D., born 4/7/67; Douglas M., born 1/14/69; Margaret Earle, born 9/29/67 (unofficially adopted, 6/1/84)

Education:

• 1954-1959 Phillips Exeter Academy
• 1959-1963 University of North Carolina
  Morehead Scholar, Phi Eta Sigma, Phi Beta Kappa (UNC Chapter President, 1962), Graduated with A.B. and honors in Botany
• 1963-1968 California Institute of Technology, Division of Biology
  National Science Foundation Graduate Fellow; Honorary Woodrow Wilson Fellow
  Major: Biochemistry - Minor: Chemistry
  Ph.D., 1968: "Studies on Plant and Animal Histones"

Professional Experience:

• 1967-1968 Instructor, Division of Biology, California Institute of Technology
• 1969-1985 Staff Member, Carnegie Institution of Washington, Dept. of Embryology
• 1979 Gosney Fellow, Division of Biology, California Institute of Technology
• 1985 Wiersma Visiting Professor of Neurobiology, California Institute of Technology
• 1978-present Professor, Department of Biology and Department of Biophysics, The Johns Hopkins University

Professional Societies:

• Society of General Physiologists: Councilor, 1981-1983; President 1988-1989; Co-organizer 1986 annual meeting; Organizer 1993 annual meeting
• American Society for Cell Biology: Councilor, 1985-88 Nominations Committee Chairman 1988-89
• AAAS

Editorial Boards:

• Current Topics in Membranes, 1988-2000; Co-editor with Arnost Kleinzeller, Dale Benos
• Developmental Biology 1978-1980
• Developmental Neuroscience 1978-1982
• Neuroscience 1975-1985
• J. Neuroscience Methods 1978-1983
• Developmental Brain Research, 1980-1994
• Molecular Brain Research, 1986-1994
• Physiological Reviews 1986-1991

Other Extramural Activities and Honors:

• Scientific Advisory Board, Searle Scholars Program, 1980-1984
• Scientific Director, Searle Scholars Program, 1996-present
• Scientific Advisory Board, Muscular Dystrophy Association, 1982-1988
• Ad hoc Member, Molecular Cytology Study Section, NIH 1980, 1981; Cell Biology Study Section, NIH 1991; Physiology Study Section, NIH, 1994.
• Javits Neuroscience Investigator Award, 1988
• Javits Neuroscience Investigator Award, 1995
• Elected a Fellow of the AAAS, 1992

Graduate Students Trained:

• H. Criss Hartzell, Professor of Anatomy, Emory University School of Medicine
• Peter N. Devreotes, Professor and Chair, Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine
• John M. Gardner, Research Scientist, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ
• Jennifer Lippincott-Schwartz, Senior Staff Scientist, NICHD, NIH
• Zaven Kaprielian, Assistant Professor of Pathology, Albert Einstein College of Medicine
• A. Malcolm Campbell, Assistant Professor of Biology, Davidson University
• Karen J. Renaud Magnet, Chief of Biochemistry, Division of Clinical Investigation, Tripler Army Medical Center, Honolulu, Hawaii.
• Joseph P. Taormino, Patent Lawyer, Hoffmann & Eitle, Munich, Germany
• Paul M. Mathews, Post-Doctoral Fellow, Harvard Medical School
• Maura L. Hamrick, Ph.D., M.D., Family Practice, Liberty, North Carolina
• M. Victor Lemas, Research Associate, Oncology, The Johns Hopkins University
• Yuanyi Feng, Post-Doctoral Fellow, Dept of Molecular Biol., Mass General Hospital.
• Thomas E. Colonna, Editor-in-Chief, Medivations
• Mitch Kostich, Shering Plough Corporation
• Long H. Huynh, Medical Student, University of Colorado School of Medicine
• Ben C. Huang, McKinsey&Company, Inc., Pittsburgh, PA

Post-Doctoral Fellows Trained:

• Aileen Ritchie, Professor of Physiology and Biophysics, U. Texas Medical School, Galveston
• Kathy Tepperman, Professor, University of Cincinnati School of Medicine
• Barry Wolitzky, Department of Molecular Genetics, Hoffmann LaRoche
• Ellen Bayne, Department of Biochemistry and Molecular Pathology, Merck Research Labs
• Matthias Chiquet, M. E. Mueller Institute for Biomechanics University of Berne, Berne, Switzerland
• Michael Tamkun, Professor of Physiology, Colorado State University
• Salvatore Carbonetto, Professor of Neurology, McGill University
• Richard L. Rotundo, Professor of Cell Biology and Anatomy, University of Miami School of Medicine
• Diana Card Linden, Associate Professor, Department of Biology, Occidental College
• Eric Wakshull, Alpha-Beta Technology, Inc., Worcester, MA
• M. John Anderson
• Norman Karin, Assoc. Prof., Dept. of Biological Sciences, University of Deleware
• Ricky Lebovitz, Law Offices of Millen, White, Zelano & Branigan, Arlington, Va.
• Kunio Takeyasu, Professor, Graduate School of Biostudies, University of Kyoto
• Anita Zot, Dept. of Biology, Eastern Michigan University, Ypsilanti, MI
• Mark Emerick, Research Associate, Department of Physiology, The Johns Hopkins University
• Bruce Kone, M.D., Renal Division, Department of Internal Medicine, University of Texas Health Sciences Center, Houston
• Paul Kessler, M.D., Genvec Inc., Rockville, MD
• Xiaoming Zhou, Research Assistant Professor of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.
• Yan Song, last known address: Dept. of Biophysics, The Johns Hopkins University, Baltimore.
• Shawn Robinson, M.D., Assistant Professor, Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, Baltimore

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