On-line confocal imaging of the events leading to structural dedifferentiation of an axonal segment into a growth cone after axotomy.

نویسندگان

  • Iman Sahly
  • Arkady Khoutorsky
  • Hadas Erez
  • Masha Prager-Khoutorsky
  • Micha E Spira
چکیده

The transformation of a transected axonal tip into a growth cone (GC) after axotomy is a critical step in the cascade of events leading to regeneration. However, the mechanisms underlying it are largely unknown. In earlier studies we reported that axotomy of cultured Aplysia neurons leads to a transient and local increase in the free intracellular Ca2+ concentration, calpain activation, and localized proteolysis of the submembranal spectrin. In a recent ultrastructural study, we reported that calpain activation is critical for the restructuring of the microtubules and neurofilaments at the cut axonal end to form a compartment in which vesicles accumulate. By using on-line confocal imaging of microtubules (MTs), actin, and vesicles in cultured Aplysia neurons, we studied the kinetics of the transformation and examined some of the mechanisms that orchestrate it. We report that perturbation of the MTs' polymerization by nocodazole inhibits the formation of an MT-based compartment in which the vesicles accumulate, yet actin repolymerization proceeds normally to form a nascent GC's lamellipodium. Nevertheless, under these conditions, the lamellipodium fails to expand and form neurites. When actin filament polymerization is inhibited by cytochalasin D or jasplakinolide, the MT-based compartment is formed and vesicles accumulate at the cut axonal end. However, a GC's lamellipodium is not formed, and the cut axonal end fails to regenerate. A growth-competent GC is formed only when MT restructuring, the accumulation of vesicles, and actin polymerization properly converge in time and space.

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Localized and transient elevations of intracellular Ca2+ induce the dedifferentiation of axonal segments into growth cones.

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عنوان ژورنال:
  • The Journal of comparative neurology

دوره 494 5  شماره 

صفحات  -

تاریخ انتشار 2006