Focal adhesion kinase signaling at sites of integrin-mediated adhesion controls axon pathfinding.
Extracellular matrix (ECM) components regulate neurite outgrowth in tissue culture and in vivo. Live imaging of phosphotyrosine (PY) signals revealed that Xenopus laevis growth cones extending on permissive ECM substrata assemble adhesive point contacts containing enriched levels of tyrosine-phosphorylated proteins. Whereas focal adhesion kinase (FAK) signaling is dispensable for the assembly of focal adhesions in non-neuronal cells, FAK activity is required for the formation of growth cone point contacts. FAK-dependent point contacts promote rapid neurite outgrowth by stabilizing lamellipodial protrusions on permissive ECM substrata. Moreover, local FAK activity is required for ECM-dependent growth cone turning in vitro, suggesting that FAK may control axon pathfinding in vivo. Consistent with this possibility, proper growth and guidance of Rohon-Beard sensory neurons and spinal commissural interneurons requires FAK activity. These findings identify FAK as a key regulator of axon growth and guidance downstream of growth cone-ECM interactions.
Robles
Estuardo
E
Department of Anatomy and Neuroscience Training Program, University of Wisconsin, 257 Bardeen Labs-SMI, 1300 University Avenue, Madison, Wisconsin 53706, USA.
Gomez
Timothy M
TM
D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology*; D001757:Blastomeres / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique / Q000379:methods; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology; D016023:Integrins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D014982:Xenopus laevis
D016326:Extracellular Matrix Proteins; D016023:Integrins; D051419:Paxillin; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases