Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating

EMBO Rep. 2001 Jul;2(7):634-40. doi: 10.1093/embo-reports/kve134. Epub 2001 Jul 3.

Abstract

Synaptic vesicle biogenesis involves the recycling of synaptic vesicle components by clathrin-mediated endocytosis from the presynaptic membrane. stoned B, a protein encoded by the stoned locus in Drosophila melanogaster has been shown to regulate vesicle recycling by interacting with synaptotagmin. We report here the identification and characterization of a human homolog of stoned B (hStnB). Human stoned B is a brain-specific protein which co-enriches with other endocytic proteins such as AP-2 in a crude synaptic vesicle fraction and at nerve terminals. A domain with homology to the medium chain of adaptor complexes binds directly to both AP-2 and synaptotagmin and competes with AP-2 for the same binding site within synaptotagmin. Finally we show that the mu 2 homology domain of hStnB stimulates the uncoating of both clathrin and AP-2 adaptors from clathrin-coated vesicles. We hypothesize that hStnB regulates synaptic vesicle recycling by facilitating vesicle uncoating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Brain Chemistry
  • Calcium-Binding Proteins*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Fractionation
  • Clathrin-Coated Vesicles / metabolism*
  • Drosophila
  • Drosophila Proteins*
  • Enzyme Inhibitors / metabolism
  • Genes, Reporter
  • Humans
  • Immunoblotting
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Synaptotagmins
  • Tissue Distribution

Substances

  • Adaptor Proteins, Vesicular Transport
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Drosophila Proteins
  • Enzyme Inhibitors
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • stnB protein, Drosophila
  • Synaptotagmins

Associated data

  • GENBANK/AF380833
  • GENBANK/AF449430