Abstract
The renal glomerular podocyte exhibits a highly arborized morphology. In comparison with the neuron, which is the best studied process-bearing cell, the podocyte major processes share many cell biological characteristics with neuronal dendrites. Both podocytes and neurons develop microtubule-based thick processes with branching morphology and both have thin actin-based projections (i.e. podocyte foot processes and dendritic spines). Formation of podocyte processes and neuronal dendrites depends on the assembly of microtubules. Because the assembly of microtubules is regulated by phosphorylation of microtubule-associated proteins, inhibition of protein phosphatases abolishes and inhibition of protein kinases promotes process formation. Podocytes and dendrites also share the machinery of intracellular traffic of membranous vesicles, as well as cytoskeletal elements, which is indispensable for the elongation of these processes. Furthermore, these two cell types share expression of various molecules working for signal transduction, transmembranous transport and intercellular contacts. Such common gene expression implies a similar transcriptional regulation in these cells. Concerning the formation of podocyte foot processes and dendritic branches, actin filaments are thought to play a central role in orchestrating the function of various molecules and the regulation of actin assembly is necessary to establish and maintain such sophisticated cellular architecture. The molecular mechanism of foot process formation seems to include Rho family small GTP-binding proteins, which are known to be responsible for the establishment of dendritic branching morphology.
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Ahola H, Heikkila E, Astrom E (2003) A novel protein, densin, expressed by glomerular podocytes. J Am Soc Nephrol 14, 1731–7.
Andrews PM (1977) The effect of vinblastine-induced microtu-bule loss on kidney podocyte morphology. Am J Anat 150, 53–61.
Apperson ML, Moon IS, Kennedy MB (1996) Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. J Neurosci 16, 6839–952.
Balda MS, Matter K (2003) Epithelial call adhesion and the regulation of gene expression. Tr ends Cell Biol 13, 310–18.
Barisoni L, Kopp JB (2003) Update in podocyte biology: Putting one’s best foot forward. Curr Opin Nephrol Hypertens 12, 251–9.
Barisoni L, Mundel P (2003) Podocyte biology and the emerging understanding of podocyte diseases. Am J Nephrol 23, 353–60.
Barletta GM, Kovari IA, Verma RK, Kerjaschki D, Holzman LB (2003) Nephrin and Neph1 co-localize at the podocyte foot process intercellular junction and form cis hetero-oligomers. J Biol Chem 278, 19 266–71.
Beltcheva O, Kontusaari S, Fetissov S et al. (2003) Alternatively used promoters and distinct elements direct tissue-specific expression of nephrin. J Am Soc Nephrol 14, 352–8.
Beltran PJ, Bixby JL, Masters BA (2003) Expression of PTPRO during mouse development suggests involvement in axono-genesis and differentiation of NT-3 and NGF-dependent neurons. J Comp Neurol 465, 384–95.
Bourdoulous S, Bourdoulous S, Orend G, MacKenna DA, Pas-qualini R, Ruoslahti E (1998) Fibronectin matrix regulates activation of RHO and CDC42 GTPases and cell cycle progression. J Cell Biol 143, 267–76.
Chiou JY, Westhead EW (1992) Okadaic acid, a protein phosphatase inhibitor, inhibits nerve growth factor-directed neurite outgrowth in PC12 cells. J Neurochem 59, 1963–6.
Cortes P, Mendez M, Riser BL et al. (2000) F-Actin fiber distribution in glomerular cells: Structural and functional implications. Kidney Int 58, 2452–61.
de Hoop MJ, Dotti CG (1993) Membrane traffic in polarized neurons in culture. J Cell Sci Suppl 17, 85–92.
Deller T, Mundel P (2000) Potential role of synaptopodin in spine motility by coupling actin to the spine apparatus. Hippocampus 10, 569–81.
Dong JM, Leung T, Manser E, Lim L (1998) cAMP-induced morphological changes are counteracted by the activated RhoA small GTPase and the Rho kinase ROKalpha. J Biol Chem 273, 22 554–62.
Dotti CG, Simons K (1990) Polarized sorting of viral glycopro-teins to the axon and dendrites of hippocampal neurons in culture. Cell 62, 63–72.
Endlich K, Kriz W, Witzgall R (2001) Update in podocyte biology. Curr Opin Nephrol Hypertens 10, 331–40.
Feoktistov I, Goldstein AE, Biaggioni I (2000) Cyclic AMP and protein kinase A stimulate Cdc42: Role of A(2) adenosine receptors in human mast cells. Mol Pharmacol 58, 903–10.
Gao FB, Brenman JE, Jan LY, Jan YN (1999) Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Gene Dev 13, 2549–61.
Gao S, Li C, Chen J et al. (2004) Rho-ROCK signal pathway regulates microtubule-based process formation of cultured podocytes: Inhibition of ROCK promoted process elongation. Nephron Exp Nephrol (in press).
Gerke P, Huber TB, Sellin L, Benzing T, Walz G (2003) Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1. J Am Soc Nephrol 14, 918–26.
Gloy J, Reitinger S, Fischer KG et al. (2000) Amino acid transporter in podocytes. Am J Physiol 278, F999–1005.
Gong CX, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K (2000a) Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. J Biol Chem 275, 5535–44.
Gong CX, Wegiel J, Lidsky T et al. (2000b) Regulation of phosphorylation of neuronal microtubule-associated proteins MAP1b and MAP2 by protein phosphatase-2A and -2B in rat brain. Brain Res 853, 299–309.
Goto H, Wakui H, Komatsuda A et al. (2003) Renal alpha-actinin-4: Purification and puromycin aminonucleoside-binding property. Nephron Exp Nephrol 93, E27–35.
Hara M, Ichida F, Higuchi A, Tanizawa T, Okada T (1984) Nephropathy associated with Charcot-Marie-Tooth disease. Int J Pediatr Nephrol 5, 99–102.
Henderson BR, Fagotto F (2002) The ins and outs of APC and beta-catenin nuclear transport. EMBO Rep 3, 834–9.
Hiraga A, Tamura S (2000) Protein phosphatase 2A is associated in an inactive state with microtubules through 2A1-specific interaction with tubulin. Biochem J 346, 433–9.
Hirose M, Ishizaki T, Watanabe N et al. (1998) Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblast-oma N1E-115 cells. J Cell Biol 141, 1625–36.
Huber TB, Schmidts M, Gerke P et al. (2003) The carboxyl terminus of Neph family members binds to the PDZ domain protein zonula occludens-1. J Biol Chem 278, 13 417–21.
Ichimura K, Kurihara H, Sakai T (2003) Actin filament organization of foot processes in rat podocytes. J Histochem Cytochem 51, 1589–600.
Ihalmo P, Palmen T, Ahola H, Valtonen E, Holthofer H (2003) Filtrin is a novel member of nephrin-like proteins. Biochem Biophys Res Commun 300, 364–70.
Inoue T, Yaoita E, Kurihara H et al. (2001) FAT is a component of glomerular slit diaphragms. Kidney Int 59, 1003–12.
Jan Y, Jan LY (2003) The control of dendrite development. Neuron 40, 229–42.
Kaplan JM, Kim SH, North KN et al. (2000) Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 24, 251–6.
Kato M, Sasaki T, Ohya T et al. (1996) Physical and functional interaction of rabphilin-3a with alpha-actinin. J Biol Chem 271, 31 775–8.
Kim K, Sirota A, Chen YH et al. (2002) Dendrite-like process formation and cytoskeletal remodeling regulated by delta-catenin expression. Exp Cell Res 275, 171–84.
Kobayashi N (2002) Mechanism of the process formation: Podocytes versus neurons. Microsc Res Tech 57, 217–23.
Kobayashi N, Mundel P (1998) A role of microtubules during the formation of cell processes in neuronal and non-neuronal cells. Cell Tissue Res 291, 163–74.
Kobayashi N, Reiser J, Kriz W, Kuriyama R, Mundel P (1998) Non-uniform microtubular polarity, established by CHO1/ MKLP1 motor protein, is necessary for process formation of podocytes. J Cell Biol 143, 1961–70.
Kobayashi N, Heid HW, Sakai T, Kriz W, Huber G, Mundel P (2000) Molecular characterization reveals the identity of microtubule-associated proteins MAP3 and MAP4. Biochem Biophys Res Commun 268, 306–9.
Kobayashi N, Mominoki K, Wakisaka H, Shimazaki Y, Matsuda S (2001a) Morphogenetic activity of extracellular matrices on cultured podocytes. Ital J Anat Embryol 106 (Suppl. 1), 423–30.
Kobayashi N, Reiser J, Schwarz K, Sakai T, Kriz W, Mundel P (2001b) Process formation of podocytes: Morphogenetic activity of microtubules and regulation by serine/threonine protein phosphatase PP2A. Histochem Cell Biol 115, 255–66.
Kos CH, Le TC, Sinha S et al. (2003) Mice deficient in alpha-actinin-4 have severe glomerular disease. J Clin Invest 111, 1683–90.
Kreidberg JA (2003) Podocyte differentiation and glomerulo-genesis. J Am Soc Nephol 14, 806–14.
Kreidberg JA, Donovan MJ, Goldstein SL et al. (1996) Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development 122, 3537–47.
Kretzler M (2002) Regulation of adhesive interaction between podocytes and glomerular basement membrane. Microsc Res Tech 57, 247–53.
Kriz W (2002) Podocyte is the major culprit accounting for the progression of chronic renal disease. Microsc Res Tech 57, 189–95.
Kriz W, Kobayashi N, Elger M (1998) New aspects of podocyte structure, function and pathology. Clin Exp Nephrol 2, 85–99.
Lemieux G, Neemeh JA (1967) Charcot-Marie-Tooth disease and nephritis. Can Med Assoc J 97, 1193–8.
Martinez MC, Ochiishi T, Majewski M, Kosik KS (2003) Dual regulation of neuronal morphogenesis by a delta-catenin- cortactin complex and Rho. J Cell Biol 162, 99–111.
Mundel P, Shankland SJ (2002) Podocyte biology and responce to injury. J Am Soc Nephrol 13, 3005–15.
Mundel P, Reiser J, Zuniga Mejia Borja A et al. (1997a) Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines. Exp Cell Res 36, 248–58.
Mundel P, Heid HW, Mundel TM, Kruger M, Reiser J, Kriz W (1997b) Synaptopodin, an actin-associated protein in telen-cephalic dendrites and in renal podocytes. J Cell Biol 139, 193–204.
Nakayama AY, Harms MB, Luo L (2000) Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J Neurosci 20, 5329–38.
Neumann H, Schweigreiter R, Yamashita T, Rosenkranz K, Wekerle H, Barde YA (2002) Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal neurons by a rho-dependent mechanism. J Neurosci 22, 854–62.
Noren NK, Liu BP, Burridge K, Kreft B (2000) p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol 150, 567–80.
Orlando RA, Takeda T, Zak B et al. (2001) The glomerular epithelial cell anti-adhesin podocalyxin associates with the actin cytoskeleton through interactions with ezrin. J Am Soc Nephrol 12, 1589–98.
Patrie KM, Drescher AJ, Goyal M, Wiggins RC, Margolis B (2001) The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes. J Am Soc Nephrol 12, 667–77.
Patrie KM, Drescher AJ, Welihinda A, Mundel P, Margolis B (2002) Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1. J Biol Chem 277, 30 183–90.
Pavenstaedt H, Kriz W, Kreztler M (2003) Cell biology of the glomerular podocyte. Physiol Rev 83, 253–307.
Peitsch WK, Hofmann I, Endlich N et al. (2003) Cell biological and biochemical characterization of drebrin complexes in mesangial cells and podocytes of renal glomeruli. J Am Soc Nephrol 14, 1452–63.
Price NE, Wadzinski B, Mumby MC (1999) An anchoring factor targets protein phosphatase 2A to brain microtubules. Brain Res Mol Brain Res 73, 68–77.
Quaggin S (2002) Transcriptional regulation of podocyte specification and differentiation. Microsc Res Tech 57, 208–11.
Rastaldi MP, Armelloni S, Berra S et al. (2003) Glomerular podocytes possess the synaptic vesicle molecule Rab3A and its specific effector Rabphilin-3a. Am J Pathol 163, 889–99.
Redmond L, Ghosh A (2001) The role of Notch and Rho GTPase signaling in the control of dendritic development. Curr Opin Neurobiol 11, 111–17.
Reiser J, Kriz W, Kretzler M, Mundel P (2000) The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol 11, 1–8.
Rodriguez OC, Schaefer AW, Mandato CA, Forscher P, Bement WM, Waterman-Storer CM (2003) Conserved microtubule- actin interactions in cell movement and morphogenesis. Nature Cell Biol 5, 599–609.
Sakai T, Kriz W (1987) The structural relationship between mesangial cells and basement membrane of the renal glomerulus. Anat Embryol 176, 373–86.
Saleem MA, Ni L, Witherden I et al. (2002) Co-localization of nephrin, podocin, and the actin cytoskeleton: Evidence for a role in podocyte foot process formation. Am J Pathol 161, 1459–66.
Schmid H, Henger A, Cohen CD et al. (2003) Gene expression profiles of podocyte-associated molecules as diagnostic markers in acquired proteinuric diseases. J Am Soc Nephrol 14, 2958–66.
Schwarz K, Simons M, Reiser J et al. (2001) Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest 108, 1621–9.
Scott EK, Reuter JE, Luo L (2003) Small GTPase Cdc42 is required for multiple aspects of dendritic morphogenesis. J Neurosci 23, 3118–23.
Sellin L, Huber TB, Gerke P, Quack I, Pavenstadt H, Walz G (2003) NEPH1 defines a novel family of podocin-interacting proteins. FASEB J 17, 115–17.
Shirato I, Sakai T, Kimura K, Tomino Y, Kriz W (1996) Cytoskel-etal changes in podocytes associated with foot process effacement in Masugi nephritis. Am J Pathol 148, 1283–96.
Simons M, Saffrich R, Reiser J, Mundel P (1999) Directed membrane transport is involved in process formation of cultured podocytes. J Am Soc Nephrol 10, 1633–9.
Somlo S, Mundel P (2000) Getting a foothold in nephrotic syndrome. Nat Genet 24, 333–5.
Sontag E, Nunbhakdi-Craig V, Lee G et al. (1999) Molecular interactions among protein phosphatase 2A, tau, and micro-tubules. J Biol Chem 274, 25 490–8.
Takai Y, Sasaki T, Matozaki T (2001) Small GTP-bindings proteins. Physiol Rev 81, 153–207.
Takeda T, McQuistan T, Orlando RA, Farquhar MG (2001) Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J Clin Invest 108, 289–301.
Togawa A, Miyoshi J, Ishizaki H et al. (1999) Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. Oncogene 18, 5373–80.
Usui J, Kurihara H, Shu Y et al. (2003) Localization of intercellular adherens junction protein p120 catenin during podocyte differentiation. Anat Embryol 206, 175–84.
Wong WT, Faulkner-Jones BE, Sanes JR, Wong RO (2000) Rapid dendritic remodeling in the developing retina: Dependence on neurotransmission and reciprocal regulation by Rac and Rho. J Neurosci 20, 5024–36.
Yamaguchi Y, Katoh H, Yasui H, Mori K, Negishi M (2001) RhoA inhibits the nerve growth factor-induced Rac1 activation through Rho-associated kinase-dependent pathway. J Biol Chem 276, 18 977–83.
Yu W, Sharp DJ, Kuriyama R, Mallik P, Baas PW (1997) Inhibition of a mitotic motor compromises the formation of dendrite-like processes from neuroblastoma cells. J Cell Biol 136, 659–68.
Yu W, Cook C, Sauter C, Kuriyama R, Kaplan PL, Baas PW (2000) Depletion of a microtubule-associated motor protein induces the loss of dendritic identity. J Neurosci 20, 5782–91.
Yu X, Malenka RC (2003) Beta-catenin is critical for dendritic morphogenesis. Nat Neurosci 6, 1169–77.
Yuan XB, Jin M, Xu X et al. (2003) Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nat Cell Biol 5, 1–8.
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Kobayashi, N., Gao, Sy., Chen, J. et al. Process formation of the renal glomerular podocyte: Is there common molecular machinery for processes of podocytes and neurons?. Anato Sci Int 79, 1–10 (2004). https://doi.org/10.1111/j.1447-073x.2004.00066.x
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DOI: https://doi.org/10.1111/j.1447-073x.2004.00066.x