AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis

Elife. 2013 Mar 5;2:e00190. doi: 10.7554/eLife.00190.

Abstract

The clathrin adaptor complex AP2 is thought to be an obligate heterotetramer. We identify null mutations in the α subunit of AP2 in the nematode Caenorhabditis elegans. α-adaptin mutants are viable and the remaining μ2/β hemicomplex retains some function. Conversely, in μ2 mutants, the alpha/sigma2 hemicomplex is localized and is partially functional. α-μ2 double mutants disrupt both halves of the complex and are lethal. The lethality can be rescued by expression of AP2 components in the skin, which allowed us to evaluate the requirement for AP2 subunits at synapses. Mutations in either α or μ2 subunits alone reduce the number of synaptic vesicles by about 30%; however, simultaneous loss of both α and μ2 subunits leads to a 70% reduction in synaptic vesicles and the presence of large vacuoles. These data suggest that AP2 may function as two partially independent hemicomplexes. DOI:http://dx.doi.org/10.7554/eLife.00190.001.

Keywords: AP2; C. elegans; apa-2; apm-2; synaptic vesicle endocytosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Protein Complex 2 / genetics
  • Adaptor Protein Complex 2 / metabolism*
  • Adaptor Protein Complex alpha Subunits / genetics
  • Adaptor Protein Complex alpha Subunits / metabolism
  • Adaptor Protein Complex beta Subunits / genetics
  • Adaptor Protein Complex beta Subunits / metabolism
  • Adaptor Protein Complex mu Subunits / genetics
  • Adaptor Protein Complex mu Subunits / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Endocytosis*
  • Exocytosis
  • Genotype
  • Phenotype
  • Synaptic Vesicles / metabolism*

Substances

  • Adaptor Protein Complex 2
  • Adaptor Protein Complex alpha Subunits
  • Adaptor Protein Complex beta Subunits
  • Adaptor Protein Complex mu Subunits
  • Caenorhabditis elegans Proteins
  • Dpy-23 protein, C elegans