The growth cone gets a grip

杨柳

Like a rock climber, a neuronal growth cone senses its substrate to identify the route that will provide the best grip. For the growth cone, this involves probing with adhesion molecules that direct cytoskeletal reorganization and movement, but how does the cell determine that a particular spot will withstand tension? On page 427, Suter and Forscher report that slight initial tension on the adhesion molecule apparently induces tyrosine kinase activity, which then stiffens the growth cone's grip through a positive-feedback mechanism.
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% y8 J5 A9 D; ]! xWhen the Aplysia growth cone adhesion molecule apCAM interacts with physically restrained beads coated with apCAM ligand, the growth cone steers across the surface of the beads. Tyrosine phosphorylation increases at sites where the cells bind to restrained beads, but not at sites with unrestrained beads. Inhibitors of myosin or Src family tyrosine kinases reduce growth cone traction on restrained beads.The authors propose that the tension from apCAM binding to restrained beads leads to Src family tyrosine kinase activation, which then promotes the strengthening of apCAM–actin linkages. The stronger linkages further increase tension, until the apCAM–actin linkage is strong enough to guide growth cone extension. Similar to the mechanisms proposed for integrin-mediated substrate interactions, this would drive growth cone migration along the path providing the best molecular grip.(Restrained beads light up migrating cell)