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ERM proteins regulate growth cone responses to Sema3A.

The Journal of comparative neurology | 2008

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.

Pubmed ID: 18651636 RIS Download

Associated grants

  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA014898-05
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS037731
  • Agency: NINDS NIH HHS, United States
    Id: NS046142
  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA014898
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS050634
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS050634-03
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS045305
  • Agency: NIAAA NIH HHS, United States
    Id: AA014898
  • Agency: NINDS NIH HHS, United States
    Id: NS037731
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS050634-01A2
  • Agency: NINDS NIH HHS, United States
    Id: NS050634
  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA014898-04S1
  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA014898-03
  • Agency: NINDS NIH HHS, United States
    Id: F30 NS046142
  • Agency: NINDS NIH HHS, United States
    Id: NS045305

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