Loss of SNAP29 impairs endocytic recycling and cell motility

PLoS One. 2010 Mar 18;5(3):e9759. doi: 10.1371/journal.pone.0009759.

Abstract

Intracellular membrane trafficking depends on the ordered formation and consumption of transport intermediates and requires that membranes fuse with each other in a tightly regulated and highly specific manner. Membrane anchored SNAREs assemble into SNARE complexes that bring membranes together to promote fusion. SNAP29 is a ubiquitous synaptosomal-associated SNARE protein. It interacts with several syntaxins and with the EH domain containing protein EHD1. Loss of functional SNAP29 results in CEDNIK syndrome (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma). Using fibroblast cell lines derived from CEDNIK patients, we show that SNAP29 mediates endocytic recycling of transferrin and beta1-integrin. Impaired beta1-integrin recycling affected cell motility, as reflected by changes in cell spreading and wound healing. No major changes were detected in exocytosis of VSVG protein from the Golgi apparatus, although the Golgi system acquired a dispersed morphology in SNAP29 deficient cells. Our results emphasize the importance of SNAP29 mediated membrane fusion in endocytic recycling and consequently, in cell motility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement*
  • Cholera Toxin / metabolism
  • Endocytosis*
  • Exocytosis
  • Fibroblasts / metabolism*
  • Golgi Apparatus / metabolism
  • Humans
  • Integrin beta1 / metabolism
  • Models, Biological
  • Phosphorylation
  • Protein Structure, Tertiary
  • Qb-SNARE Proteins / metabolism*
  • Qc-SNARE Proteins / metabolism*
  • Transferrin / chemistry
  • Wound Healing

Substances

  • Integrin beta1
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • SNAP29 protein, human
  • Transferrin
  • Cholera Toxin