Domain requirements for an endocytosis-independent, isoform-specific function of dynamin-2

Fabienne Soulet, Sandra L. Schmid, Hanna Damke

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Endocytosis is inhibited by overexpression of either dynamin-1 or dynamin-2 mutants because both isoforms form heterotetramers with endogenous dynamin-2 and interfere with its function. By contrast, other phenotypes, which are specifically triggered by overexpression of dynamin-2, but not dynamin-1 are likely to reflect endocytosis-independent, dynamin-2-specific functions and/or interactions. Using Dyn2/Dyn1 chimeras, we explored the structural requirements for a readily quantifiable, isoform-specific function of dynamin-2, the activation of caspase-3 to trigger apoptosis. Strikingly, swapping the highly homologous GTPase domain of dynamin-2 into dynamin-1 was sufficient to confer caspase-3 activation. Moreover, assembly-defective mutations in GED, dynamin's GAP/assembly domain, that inhibit endocytosis enhance caspase-3 activation. Thus, this dynamin-2-specific function is mechanistically distinct from and independent of its role in endocytosis. These findings have important implications for interpreting dynamin-2 dependent phenotypes in overexpression studies.

Original languageEnglish (US)
Pages (from-to)3539-3545
Number of pages7
JournalExperimental Cell Research
Volume312
Issue number18
DOIs
StatePublished - Nov 1 2006

Keywords

  • Apoptosis
  • Caspase 3
  • Dynamin
  • Endocytosis
  • GTPase
  • p53

ASJC Scopus subject areas

  • Cell Biology

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