Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone

Dotan Kamber, Hadas Erez, Micha E. Spira*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

The transformation of a cut axonal end into a growth cone (GC), after axotomy, is a critical event in the cascade leading to regeneration. In an earlier series of studies we analyzed the cellular cascades that transform a cut axonal end into a competent GC. We found that axotomy of cultured Aplysia neurons leads to a transient elevation of the free intracellular Ca2+ concentration ([Ca2+]i), calpain activation and localized proteolysis of submembranal spectrin. These events are associated with the formation of distinct microtubule (MT) based vesicle traps that accumulate anterogradely transported vesicles that fuse with the spectrin free plasma membrane in support of the growth process (Erez, H., Malkinson, G., Prager-Khoutorsky, M., De Zeeuw, C.I., Hoogenraad, C.C., and Spira, M.E. 2007. Formation of microtubule-based traps controls the sorting and concentration of vesicles to restricted sites of regenerating neurons after axotomy. J. Cell Biol. 176: 497-507.; Erez, H., and Spira, M.E. 2008. Local self-assembly mechanisms underlie the differential transformation of the proximal and distal cut axonal ends into functional and aberrant growth cones. J. Comp. Neurol. 507: spc1.). Here we report that under conditions that limit calcium influx into the cut axonal end, axotomy leads to the formation of endbulbs (EBs) rather than to competent GCs. Under these conditions typical MT based vesicle traps are not formed, and Golgi derived vesicles concentrate at the very tip of the cut axon. Since under these conditions the spectrin barrier is not cleaved, vesicle fusion with the plasma membrane and actin polymerization are retarded and growth processes are impaired. We conclude that the immediate assembly of competent GC or an EB after axotomy is the outcome of autonomous local events that are shaped by the magnitudes of the [Ca2+]i gradients at the site of injury.

Original languageAmerican English
Pages (from-to)112-125
Number of pages14
JournalExperimental Neurology
Volume219
Issue number1
DOIs
StatePublished - Sep 2009

Bibliographical note

Funding Information:
This study was supported by grant No. 2007182 from the United States–Israel Binational Science Foundation (BSF), Jerusalem, Israel. Parts of the work were done at the Charles E. Smith Family and Prof. Elkes Laboratory for Collaborative Research in Psychobiology. We thank Dr. E. Shapira and A. Dormann for technical help in preparing mRNAs, and complementary electron microscope studies. M.E. Spira is the Levi DeViali Prof. in Neurobiology.

Keywords

  • Actin
  • Aplysia
  • Calcium
  • Growth cone
  • Microtubules
  • Regeneration
  • Vesicles transport

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