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J. Cell Biol. 183 (5): 949-961

Copyright © 2008 by the Rockefeller University Press.

Article

Collective cell migration requires vesicular trafficking for chemoattractant delivery at the trailing edge

Paul W. Kriebel1, Valarie A. Barr1, Erin C. Rericha1,3, Guofeng Zhang2, , and Carole A. Parent1

1 Laboratory of Cellular and Molecular Biology, National Cancer Institute, and 2 Division of Bioengineering and Physical Sciences, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892
3 Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, MD 20742

Correspondence to Carole A. Parent: parentc{at}mail.nih.gov

Abstract: Chemoattractant signaling induces the polarization and directed movement of cells secondary to the activation of multiple effector pathways. In addition, chemotactic signals can be amplified and relayed to proximal cells via the synthesis and secretion of additional chemoattractant. The mechanisms underlying such remarkable features remain ill defined. We show that the asymmetrical distribution of adenylyl cyclase (ACA) at the back of Dictyostelium discoideum cells, an essential determinant of their ability to migrate in a head-to-tail fashion, requires vesicular trafficking. This trafficking results in a local accumulation of ACA-containing intracellular vesicles and involves intact actin, microtubule networks, and de novo protein synthesis. We also show that migrating cells leave behind ACA-containing vesicles, likely secreted as multivesicular bodies and presumably involved in the formation of head-to-tail arrays of migrating cells. We propose that similar compartmentalization and shedding mechanisms exist in mammalian cells during embryogenesis, wound healing, neuron growth, and metastasis.

Abbreviations used in this paper: ACA, adenylyl cyclase; cAR, cAMP receptor; CHC, clathrin heavy chain; CHX, cycloheximide; CLC, clathrin light chain; CRAC, cytosolic regulator of ACA; LatA, latrunculin A; MTOC, microtubule organizing center; MVB, multivesicular body; MyoJ, myosin J; Noco, Nocodazole; PI3K, phosphatidylinositol-3-kinase; ROI, region of interest; WT, wild type.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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