Antagonistic effects of Rnd1 and RhoD GTPases regulate receptor activity in Semaphorin 3A-induced cytoskeletal collapse.
The semaphorins are a large protein family that is involved in the patterning of neuronal connections in the developing nervous system of both vertebrates and invertebrates. The chemorepulsive axon guidance signal Semaphorin 3A (Sema3A) induces the depolymerization of actin filaments and the collapse of sensory growth cones by activating a receptor complex that contains a plexin as the signal-transducing subunit. Here we show that, of a large number of GTPases tested, only Rnd1 and RhoD bind the cytoplasmic domain of Plexin-A1. Recruitment of active Rnd1 is sufficient to trigger signaling by Plexin-A1, even in the absence of Sema3A, and initiates cytoskeletal collapse by activating its cytoplasmic domain. RhoD, in contrast, blocks Plexin-A1 activation by Rnd1 and repulsion of sympathetic axons by Sema3A. Thus, the antagonism of two GTPases regulates the activity of the Sema3A receptor, and activation by Rnd1 appears to be an essential step in signaling by Plexin-A1.
Zanata
Silvio M
SM
Molecular Neurogenetics Laboratory, Department of Neurochemistry, Max-Planck-Institute for Brain Research, D-60528 Frankfurt, Germany.
Hovatta
Iiris
I
Rohm
Beate
B
Püschel
Andreas W
AW
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D019556:COS Cells; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039942:Neuropilin-1; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D040121:Semaphorin-3A; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D006023:Glycoproteins; D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; D011506:Proteins; C491772:RND1 protein, human; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; D039942:Neuropilin-1; C491334:Rhod protein, mouse; D020558:GTP Phosphohydrolases; D020741:rho GTP-Binding Proteins