title: Collective cell migration requires vesicular trafficking for chemoattractant delivery at the trailing edge.
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.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Kriebel
authors.forename: Valarie A
authors.initials: VA
authors.lastname: Barr
authors.forename: Erin C
authors.initials: EC
authors.lastname: Rericha
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Carole A
authors.initials: CA
authors.lastname: Parent
mesh_terms: D000199:Actins / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis; D002966:Clathrin / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D011992:Endosomes / Q000201:enzymology; D008870:Microtubules / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D022161:Transport Vesicles / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D000199:Actins; D002630:Chemotactic Factors; D002966:Clathrin; D011993:Recombinant Fusion Proteins; D000262:Adenylyl Cyclases