The semaphorin 3A receptor may directly regulate the activity of small GTPases.
The axon guidance signal semaphorin 3A induces the rapid collapse of growth cones by activating a receptor complex that contains neuropilin-1 as the ligand-binding and a plexin as the signal-transducing subunit. Here we show that plexins bind Rho-like GTPases and may directly regulate their activity. The cytoplasmic domain of plexins shows sequence similarity to GTPase activating proteins (GAPs) and mutation of two arginines that correspond to the catalytic residues of Ras GAPs inactivates plexin-A1. Our data suggest that plexins may be integral membrane proteins with an intrinsic GAP activity that is essential for their ability to induce growth cone collapse.
Rohm
B
B
Molecular Neurogenetics Laboratory, Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstr. 46, D-60528, Frankfurt, Germany.
Rahim
B
B
Kleiber
B
B
Hovatta
I
I
Püschel
A W
AW
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D039942:Neuropilin-1; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D014162:Transfection; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C091529:plexin; D039942:Neuropilin-1; D001120:Arginine; D020741:rho GTP-Binding Proteins