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Nat Cell Biol. 2016 Jan;18(1):54-64. doi: 10.1038/ncb3287. Epub 2015 Dec 7.

Persistent cell migration and adhesion rely on retrograde transport of β(1) integrin.

Author information

1
Institut Curie, PSL Research University, Endocytic Trafficking and Therapeutic Delivery group, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
2
CNRS UMR3666, 75005 Paris, France.
3
INSERM U1143, 75005 Paris, France.
4
Institut Curie, PSL Research University, Molecular Mechanisms of Intracellular Transport group, 75248 Paris Cedex 05, France.
5
CNRS UMR144, 75005 Paris, France.
6
Institut Curie, PSL Research University, Systems Cell Biology of Cell Polarity and Cell Division, 75248 Paris Cedex 05, France.
7
Institut Curie, PSL Research University, Proteases and Immunity group, 75248 Paris Cedex 05, France.
8
INSERM U932, 75005 Paris, France.
9
Institut Curie, PSL Research University, CNRS UMR 3215, INSERM U934, 75248 Paris Cedex 05, France.
10
Ecole Polytechnique, CNRS UMR7654, route de Saclay, 91128 Palaiseau Cedex, France.
11
Institut Curie, PSL Research University, Membrane Dynamics and Mechanics of Intracellular Signaling group, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
12
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, M13 9PT Manchester, UK.

Abstract

Integrins have key functions in cell adhesion and migration. How integrins are dynamically relocalized to the leading edge in highly polarized migratory cells has remained unexplored. Here, we demonstrate that β1 integrin (known as PAT-3 in Caenorhabditis elegans), but not β3, is transported from the plasma membrane to the trans-Golgi network, to be resecreted in a polarized manner. This retrograde trafficking is restricted to the non-ligand-bound conformation of β1 integrin. Retrograde trafficking inhibition abrogates several β1-integrin-specific functions such as cell adhesion in early embryonic development of mice, and persistent cell migration in the developing posterior gonad arm of C. elegans. Our results establish a paradigm according to which retrograde trafficking, and not endosomal recycling, is the key driver for β1 integrin function in highly polarized cells. These data more generally suggest that the retrograde route is used to relocalize plasma membrane machinery from previous sites of function to the leading edge of migratory cells.

PMID:
26641717
DOI:
10.1038/ncb3287
[Indexed for MEDLINE]

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