Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

Nat Commun. 2014 Oct 31;5:5325. doi: 10.1038/ncomms6325.

Abstract

Reorganization of the actin cytoskeleton is an early cellular response to various extracellular signals. Sema3A, a repulsive axon guidance molecule, induces the reorganization of actin cytoskeleton in the growth cones. Collapsin response mediator protein 1 (CRMP1) mediates the intracellular Sema3A signalling through its Ser522 phosphorylation. Here we show that UNC-33, CRMP1 C. elegans homologue, interacts with FLN-1, an actin-binding Filamin-A orthologue. In nematodes, this interaction participates in the projection of DD/VD motor neurons. CRMP1 binds both the actin-binding domain and the last immunoglobulin-like repeat of Filamin-A. The alanine mutants of Filamin-A or CRMP1 in their interacting residues suppress the Sema3A repulsion in neurons. Conversely, a phosphor-mimicking mutant CRMP1(Ser522Asp) enhances the Sema3A response. Atomic-force microscopy analysis reveals that the V-shaped Filamin-A changes to a condensed form with CRMP1(Ser522Asp). CRMP1(Ser522Asp) weakens the F-actin gelation crosslinked by Filamin-A. Thus, phosphorylated CRMP1 may remove Filamin-A from the actin cytoskeleton to facilitate its remodelling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Filamins / metabolism*
  • Growth Cones / metabolism*
  • HEK293 Cells
  • Humans
  • Mice, Inbred C57BL
  • Nerve Growth Factors / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Phosphoproteins / metabolism
  • Rats, Wistar
  • Semaphorin-3A / metabolism

Substances

  • Actins
  • Caenorhabditis elegans Proteins
  • FLN-1 protein, C elegans
  • Filamins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Semaphorin-3A
  • collapsin response mediator protein-1
  • unc-33 protein, C elegans