CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane.
Close homolog of L1 (CHL1) is a transmembrane cell adhesion molecule with unique developmental functions in cortical neuronal positioning and dendritic projection within the L1 family, as well as shared functions in promotion of integrin-dependent neurite outgrowth and semaphorin3A (Sema3A)-mediated axon repulsion. The molecular mechanisms by which CHL1 mediates these diverse functions are obscure. Here it is demonstrated using a cytofluorescence assay that CHL1 is able to recruit ezrin, a member of the ezrin-radixin-moesin (ERM) family of filamentous actin binding proteins to the plasma membrane, and that this requires a membrane-proximal motif (RGGKYSV) in the CHL1 cytoplasmic domain. This sequence in CHL1 is shown to have novel functions necessary for Sema3A-induced growth cone collapse and CHL1-dependent neurite outgrowth and branching in cortical embryonic neurons. In addition, stimulation of haptotactic cell migration and cellular adhesion to fibronectin by CHL1 depends on the CHL1/ERM recruitment motif. These findings suggest that a direct or indirect interaction between CHL1 and ERM proteins mediates Sema3A-induced growth cone collapse as well as neurite outgrowth and branching, which are essential determinants of axon guidance and connectivity in cortical development.
Schlatter
Monika C
MC
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA.
Buhusi
Mona
M
Wright
Amanda G
AG
Maness
Patricia F
PF
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian; D005353:Fibronectins / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016501:Neurites / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D040121:Semaphorin-3A / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D000099149:Ezrin
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005353:Fibronectins; D049452:Green Fluorescent Proteins; D040121:Semaphorin-3A; D014157:Transcription Factors; D000099149:Ezrin; C490649:Chl1 protein, mouse; C513242:Etv5 protein, mouse