Journal
EXPERIMENTAL CELL RESEARCH
Volume 317, Issue 13, Pages 1817-1829Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.04.016
Keywords
SNARE; Integrin; Podosome; Membrane fusion; Recycling endosome; Migration
Categories
Funding
- National Health and Medical Research Council of Australia
- Children's Hospital Burns Research Institute
- Burns Trust
- University of Queensland
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The ability of cells to adhere, spread and migrate is essential to many physiological processes, particularly in the immune system where cells must traffic to sites of inflammation and injury. By altering the levels of individual components of the VAMP3/Stx4/SNAP23 complex we show here that this SNARE complex regulates efficient macrophage adhesion, spreading and migration on fibronectin. During cell spreading this complex mediates the polarised exocytosis of VAMP3-positive recycling endosome membrane into areas of membrane expansion, where VAMP3's surface partner Q-SNARE complex Stx4/SNAP23 was found to accumulate. Lowering the levels of VAMP3 in spreading cells resulted in a more rounded cell morphology and most cells were found to be devoid of the typical ring-like podosome superstructures seen normally in spreading cells. In migrating cells lowering VAMP3 levels disrupted the polarised localisation of podosome clusters. The reduced trafficking of recycling endosome membrane to sites of cell spreading and the disorganised podosome localisation in migrating macrophages greatly reduced their ability to persistently migrate on fibronectin. Thus, this important SNARE complex facilitate S macrophage adhesion, spreading, and persistent macrophage migration on fibronectin through the delivery of VAMP3-positive membrane with its cargo to expand the plasma membrane and to participate in organising adhesive podosome structures. (C) 2011 Elsevier Inc. All rights reserved.
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