Synaptopodin: An Actin-associated Protein in Telencephalic Dendrites and Renal Podocytes

Journal of Cell Biology - Tập 139 Số 1 - Trang 193-204 - 1997
Peter Mündel1,2, Hans Heid1,2, Thomas M. Mundel1,2, Meike Krüger1,2, Jochen Reiser1,2, Wilhelm Kriz1,2
1*Department of Anatomy and Cell Biology, University of Heidelberg, D-69120 Heidelberg, Germany; and ‡Division of Cell Biology, German Cancer Research Center, D-69120 Heidelberg, Germany
2Department of Anatomy and Cell Biology, University of Heidelberg, D-69120, Heidelberg, Germany

Tóm tắt

Synaptopodin is an actin-associated protein of differentiated podocytes that also occurs as part of the actin cytoskeleton of postsynaptic densities (PSD) and associated dendritic spines in a subpopulation of exclusively telencephalic synapses. Amino acid sequences determined in purified rat kidney and forebrain synaptopodin and derived from human and mouse brain cDNA clones show no significant homology to any known protein. In particular, synaptopodin does not contain functional domains found in receptor-clustering PSD proteins. The open reading frame of synaptopodin encodes a polypeptide with a calculated Mr of 73.7 kD (human)/74.0 kD (mouse) and an isoelectric point of 9.38 (human)/9.27 (mouse). Synaptopodin contains a high amount of proline (∼20%) equally distributed along the protein, thus virtually excluding the formation of any globular domain. Sequence comparison between human and mouse synaptopodin revealed 84% identity at the protein level. In both brain and kidney, in vivo and in vitro, synaptopodin gene expression is differentiation dependent. During postnatal maturation of rat brain, synaptopodin is first detected by Western blot analysis at day 15 and reaches maximum expression in the adult animal. The exclusive synaptopodin synthesis in the telencephalon has been confirmed by in situ hybridization, where synaptopodin mRNA is only found in perikarya of the olfactory bulb, cerebral cortex, striatum, and hippocampus, i.e., the expression is restricted to areas of high synaptic plasticity. From these results and experiments with cultured cells we conclude that synaptopodin represents a novel kind of proline-rich, actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and podocyte foot processes.

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Tài liệu tham khảo

Adler, 1992, Characterization of glomerular epithelial cell matrix receptors, Am J Pathol, 141, 571

Bentley, 1994, Cytoskeletal events in growth cone steering, Curr Opin Neurobiol, 4, 43, 10.1016/0959-4388(94)90030-2

Bedford, 1997, FBP WW domains and the Abl SH3 domain bind to a specific class of proline rich ligands, EMBO (Eur Mol Biol Organ) J, 9, 2376, 10.1093/emboj/16.9.2376

Bork, 1994, The WW domain. A signalling site in dystrophin?, Trends Biochem Sci, 19, 531, 10.1016/0968-0004(94)90053-1

Castets, 1996, A novel calmodulin-binding protein, belonging to the WD-repeat family, is localized in dendrites of a subset of CNS neurons, J Cell Biol, 134, 1051, 10.1083/jcb.134.4.1051

Cheng, 1994, Block of induction and maintenance of calcium-induced LTP by inhibition of protein kinase C in postsynaptic neuron in hippocampal CA1 region, Brain Res, 646, 230, 10.1016/0006-8993(94)90083-3

Cid-Arregui, 1995, Nocodazole-dependent transport, and Brefeldin A-sensitive processing and sorting, of newly synthesized membrane proteins in cultured neurons, J Neurosci, 15, 4259, 10.1523/JNEUROSCI.15-06-04259.1995

Cybulsky, 1990, Extracellular matrix regulates proliferation and phospholipid turnover in glomerular epithelial cells, Am J Physiol, 259, F326

Dailey, 1996, The dynamics of dendritic structures in developing hippocampal slices, J Neurosci, 16, 2983, 10.1523/JNEUROSCI.16-09-02983.1996

Drenckhahn, 1988, Ultrastructural organization of contractile and cytoskeletal proteins in glomerular podocytes of chicken, rat, and man, Lab Invest, 59, 673

Einbond, 1996, Towards prediction of cognate complexes between the WW domain and proline-rich ligands, FEBS (Fed Eur Biochem Soc) Lett, 384, 1, 10.1016/0014-5793(96)00263-3

Garner, 1996, Synaptic proteins and the assembly of synaptic junctions, Trends Cell Biol, 6, 429, 10.1016/S0962-8924(96)10036-2

Garner, 1988, Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites, Nature (Lond), 336, 674, 10.1038/336674a0

Haffner, 1995, Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament associated protein VASP, EMBO (Eur Mol Biol Organ) J, 14, 19, 10.1002/j.1460-2075.1995.tb06971.x

Heid, 1994, Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein), Differentiation, 58, 113, 10.1046/j.1432-0436.1995.5820113.x

Herb, 1997, Prominent dendritic localizaiton in forebrain neurons of a novel mRNA and its product, dendrin, Mol Cell Neurosci, 8, 367, 10.1006/mcne.1996.0594

Herzog, 1978, Fractionation of brain microtubule-associated proteins. Isolation of two different proteins which stimulate tubulin polymerization in vitro, Eur J Biochem, 92, 1, 10.1111/j.1432-1033.1978.tb12716.x

Jat, 1991, Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse, Proc Natl Acad Sci USA, 88, 5096, 10.1073/pnas.88.12.5096

Kennedy, 1993, The postsynaptic density, Curr Opin Neurobiol, 3, 732, 10.1016/0959-4388(93)90145-O

Kornau, 1995, Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95, Science (Wash DC), 269, 1737, 10.1126/science.7569905

Kozak, 1989, The scanning model for translation: an update, J Cell Biol, 108, 229, 10.1083/jcb.108.2.229

Kriz, 1996, Progressive renal failure: inability of podocytes to replicate and the consequences for development of glomerulosclerosis, Nephrol Dial Transplant, 11, 1738

Matus, 1982, High actin concentrations in brain synaptic spines and postsynaptic densities, Proc Natl Acad Sci USA, 79, 7590, 10.1073/pnas.79.23.7590

Monyer, 1992, Heterodimeric NMDA receptors: molecular and functional distinction of subtypes, Science (Wash DC), 256, 1217, 10.1126/science.256.5060.1217

Mundel, 1995, Structure and function of podocytes: an update, Anat Embryol, 192, 385, 10.1007/BF00240371

Mundel, 1991, Podocytes in glomerulus of rat kidney express a characteristic 44 kD protein, J Histochem Cytochem, 39, 1047, 10.1177/39.8.1856454

Mundlos, 1993, Nuclear localization of the protein encoded by the Wims' tumor gene WT1 in embryonic and adult tissues, Development, 119, 1329, 10.1242/dev.119.4.1329

Papa, 1995, Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons, J Neurosci, 12, 1, 10.1523/JNEUROSCI.15-01-00001.1995

Quinlan, 1996, Postsynaptic mechanisms for bidirectional control of MAP2 phosphorylation by glutamate receptors, Neuron, 16, 357, 10.1016/S0896-6273(00)80053-7

Reinhard, 1992, The 46/50 KD phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts, EMBO (Eur Mol Biol Organ) J, 11, 2063, 10.1002/j.1460-2075.1992.tb05264.x

Reinhard, 1995, The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins, EMBO (Eur Mol Biol Organ) J, 14, 1583, 10.1002/j.1460-2075.1995.tb07146.x

Rosenmund, 1993, Calcium-induced actin depolymerization reduces NMDA channel activity, Neuron, 10, 805, 10.1016/0896-6273(93)90197-Y

Rybakova, 1996, A new model for the interaction of dystrophin with F-actin, J Cell Biol, 135, 661, 10.1083/jcb.135.3.661

Schäfer, 1994, Identification of the ubiquitous human desmoglein, Dsg2, and the expression catalogue of the desmoglein subfamily of desmosomal cadherins, Exp Cell Res, 222, 269

Sheng, 1996, PDZs and receptor/channel clustering: rounding up the latest suspects, Neuron, 17, 575, 10.1016/S0896-6273(00)80190-7

Shirato, 1996, Cytoskeletal changes in podocytes associated with foot process effacement in Masugi nephritis, Am J Pathol, 148, 1283

Wyszynski, 1997, Competitive binding of α actinin and calmodulin to the NMDA receptor, Nature (Lond), 385, 439, 10.1038/385439a0

Ziv, 1996, Evidence for a role of dendritic filopodia in synaptogenesis and spine formation, Neuron, 17, 91, 10.1016/S0896-6273(00)80283-4

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Journal of Cell Biology

Tập 139 Số 1

193-204

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