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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Pediatr+Nephrol 2014 ; 29 (4): 751-5 Nephropedia Template TP
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Semaphorin3a signaling, podocyte shape and glomerular disease #MMPMID24464477
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Pediatr Nephrol 2014[Apr]; 29 (4): 751-5 PMID24464477show ga
Semaphorin3a (sema3a), a member of class 3 semaphorins, is a guidance protein that regulates angiogenesis, branching morphogenesis, axon growth and cell migration, and has pleiotropic roles on organogenesis, immune response and cancer. Sema3a is secreted by podocytes and is required for normal kidney patterning and glomerular filtration barrier development. We recently discovered that after completion of kidney development Sema3a gain-of-function in podocytes leads to proteinuric glomerular disease in mice. Excess sema3a causes foot process effacement, glomerular basement lamination and endothelial damage in vivo, and disrupts podocyte shape cell autonomously by down-regulating nephrin and inhibiting ?v?3 integrin. We identified a novel direct interaction between nephrin and plexinA1, the sema3a signaling receptor. Nephrin-plexinA1 interaction links the slit-diaphragm signaling complex to extracellular sema3a signals. Hence, sema3a functions as an extracellular negative regulator of the structure and function of the glomerular filtration barrier.