Real time imaging of calcium-induced localized proteolytic activity after axotomy and its relation to growth cone formation

Daniel Gitler, Micha E. Spira

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130 Scopus citations

Abstract

The emergence of a neuronal growth cone from a transected axon is a necessary step in the sequence of events that leads to successful regeneration. Yet, the molecular mechanisms underlying its formation after axotomy are unknown. In this study, we show by real time imaging of the free intracellular Ca2+ concentration, of proteolytic activity, and of growth cone formation that the activation of localized and transient Ca2+- dependent proteolysis is a necessary step in the cascade of events that leads to growth cone formation. Inhibition of this proteolytic activity by calpeptin, a calpain inhibitor, abolishes growth cone formation. We suggest that calpain plays a central role in the reorganization of the axon's cytoskeleton during its transition from a stable differentiated structure into a dynamically extending growth cone.

Original languageEnglish
Pages (from-to)1123-1135
Number of pages13
JournalNeuron
Volume20
Issue number6
DOIs
StatePublished - 1 Jan 1998

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