The activity of the plexin-A1 receptor is regulated by Rac.
Plexins constitute a large family of transmembrane proteins that act as receptors for the semaphorin family of ligands. They are best known for their role in growth cone guidance, although they also are widely expressed outside the nervous system. Plexins are thought to control axon guidance by modifying the growth cone cytoskeleton, and Rho GTPases have been strongly implicated in this response. However, the exact contribution of Rho proteins is unclear. Sema3A/Plexin-A1-induced growth cone collapse, for example, requires Rac activity, which is a surprising result given that this GTPase is usually associated with membrane protrusions. We show here that Sema3A-induced collapse of COS-7 cells expressing Plexin-A1 also requires Rac but not Rho activity and that the cytoplasmic tail of Plexin-A1 interacts directly with activated Rac. However, collapse induced by a constitutively activated version of Plexin-A1 does not require Rac. We propose a novel function for Rac, namely that it acts upstream of Plexin-A1 during semaphoring-induced collapse, to regulate the activity of the receptor.
Turner
Laura J
LJ
MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Department of Biochemistry and Molecular Biology, Cancer Research UK, Oncogene and Signal Transduction Group, University College London, Gower Street, London, WC1E 6BT, United Kingdom.
Nicholls
Sarah
S
Hall
Alan
A
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002645:Chickens; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis; D007163:Immunosorbent Techniques; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D017354:Point Mutation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D040121:Semaphorin-3A / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection; D020798:Two-Hybrid System Techniques; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology*
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D040121:Semaphorin-3A; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins