Differential curvature sensing and generating activities of dynamin isoforms provide opportunities for tissue-specific regulation

Ya Wen Liu, Sylvia Neumann, Rajesh Ramachandran, Shawn M. Ferguson, Thomas J. Pucadyil, Sandra L. Schmid

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Dynamin 1 (Dyn1) and Dyn2 are neuronal and ubiquitously expressed isoforms, respectively, of the multidomain GTPase required for clathrin-mediated endocytosis (CME). Although they are 79% identical, Dyn1 and Dyn2 are not fully functionally redundant. Through direct measurements of basal and assembly-stimulated GTPase activities, membrane binding, self-assembly, and membrane fission on planar and curved templates, we have shown that Dyn1 is an efficient curvature generator, whereas Dyn2 is primarily a curvature sensor. Using Dyn1/Dyn2 chimeras, we identified the lipid-binding pleckstrin homology domain as being responsible for the differential in vitro properties of these two isoforms. Remarkably, their in vitro activities were reversed by a single amino acid change in the membrane-binding variable loop 3. Reconstitution of KO mouse embryo fibroblasts showed that both the pleckstrin homology and the Pro/Arg-rich domains determine the differential abilities of these two isoforms to support CME. These domains are specific to classical dynamins and are involved in regulating their activity. Our findings reveal opportunities for fundamental differences in the regulation of Dyn1, which mediates rapid endocytosis at the synapse, vs. Dyn2, which regulates early and late events in CME in nonneuronal cells.

Original languageEnglish (US)
Pages (from-to)E234-E242
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number26
DOIs
StatePublished - Jun 28 2011

Keywords

  • Curvature generation
  • Membrane remodeling
  • Protein-membrane interactions
  • Synaptic vesicle recycling

ASJC Scopus subject areas

  • General

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