title: I-BAR protein antagonism of endocytosis mediates directional sensing during guided cell migration.
abstract: Although directed cellular migration facilitates the coordinated movement of cells during development and repair, the mechanisms regulating such migration remain poorly understood. Missing-in-metastasis (MIM) is a defining member of the inverse Bin/Amphiphysin/Rvs domain (I-BAR) subfamily of lipid binding, cytoskeletal regulators whose levels are altered in a number of cancers. Here, we provide the first genetic evidence that an I-BAR protein regulates directed cell migration in vivo. Drosophila MIM (dmim) is involved in Drosophila border cell migration, with loss of dmim function resulting in a lack of directional movement by the border cell cluster. In vivo endocytosis assays combined with genetic analyses demonstrate that the dmim product regulates directed cell movement by inhibiting endocytosis and antagonizing the activities of the CD2-associated protein/cortactin complex in these cells. These studies demonstrate that DMIM antagonizes pro-endocytic components to facilitate polarity and localized guidance cue sensing during directional cell migration.
authors.affiliation: Program in Epithelial Biology and Cancer Biology Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Quinones
authors.forename: Janet
authors.initials: J
authors.lastname: Jin
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Oro
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000502:physiology*; D051356:Cortactin / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding
chemical_list: C528411:Cindr protein, Drosophila; D051356:Cortactin; D029721:Drosophila Proteins; C549400:MIM protein, Drosophila; D008840:Microfilament Proteins; D000217:Acyltransferases; C456023:endophilin A, Drosophila; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
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