ERM proteins regulate growth cone responses to Sema3A.
Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue Semaphorin 3A (Sema3A). We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1, and its coreceptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A.
Mintz
C David
CD
Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Carcea
Ioana
I
McNickle
Daniel G
DG
Dickson
Tracey C
TC
Ge
Yongchao
Y
Salton
Stephen R J
SR
Benson
Deanna L
DL
D000199:Actins / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D002645:Chickens; D003598:Cytoskeletal Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020439:Growth Cones / Q000502:physiology*; D051379:Mice; D009154:Mutation; D010957:Plasmids; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099149:Ezrin
D000199:Actins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; D014157:Transcription Factors; D000099149:Ezrin; C513242:Etv5 protein, mouse; C488217:Sema3a protein, mouse