Focal adhesion kinase functions downstream of Sema3A signaling during axonal remodeling.
Axon refinement is a necessary event for sculpting the final wiring of neural circuits. Although some factors have been identified that cause axonal arbor remodeling, the molecular pathways transducing these extracellular signals to adhesion disassembly and the cytoskeleton are poorly understood. Here we show that conditional ablation of Focal adhesion kinase (Fak) abolishes axon remodeling induced by Semaphorin-3A (Sema3A) in hippocampal neurons. Sema3A elicits divergent effects on different tyrosine residues of FAK: it increases phosphorylation of Tyr397, the kinase domain and the tyrosine residue 925, and decreases phosphorylation of Tyr407 and Tyr861. Moreover, Sema3A mediates mechanisms that contribute to the disassembly of adhesion contacts in a FAK-dependent manner: tyrosine phosphorylation of alpha-actinin and FAKY925 that decreases FAK-Paxillin interaction. Altogether, our results provide novel insights into the spatiotemporal dynamics of FAK activation mediated by Sema3A and on its interaction with its downstream effectors: Paxillin and alpha-actinin in neurons.
Instituto de Neurociencias de Alicante, CSIC & Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain.
Mariola R
MR
Chacón
Gloria
G
Fernández
Beatriz
B
Rico
D000185:Actinin / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004791:Enzyme Inhibitors; D051419:Paxillin; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D000185:Actinin; D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases