title: Novel protein Callipygian defines the back of migrating cells.
abstract: Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or "clustered," to the cell rear is immobile, but when polarity is disrupted, it disperses throughout the membrane and responds to uniform chemoattractant stimulation by transiently localizing to the cytosol. These behaviors require a pleckstrin homology-domain membrane tether and a WD40 clustering domain, which can also direct other membrane proteins to the back. Fragments of CynA lacking the pleckstrin homology domain, which are normally found in the cytosol, localize to the lagging edge membrane when coexpressed with full-length protein, showing that CynA clustering is mediated by oligomerization. Cells lacking CynA have aberrant lateral protrusions, altered leading-edge morphology, and decreased directional persistence, whereas those overexpressing the protein display exaggerated features of polarity. Consistently, actin polymerization is inhibited at sites of CynA accumulation, thereby restricting protrusions to the opposite edge. We suggest that the mutual antagonism between CynA and regions of responsiveness creates a positive feedback loop that restricts CynA to the rear and contributes to the establishment of the cell axis.
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Kristen F
authors.initials: KF
authors.lastname: Swaney
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: Jane
authors.initials: J
authors.lastname: Borleis
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, MD 21218.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Iglesias
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; pnd@jhmi.edu.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Devreotes
mesh_terms: D000199:Actins / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D022081:Cell Surface Extensions / Q000187:drug effects / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology* / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D010716:Phosphatidylinositols / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D002630:Chemotactic Factors; D010716:Phosphatidylinositols; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins
keywords: Dictyostelium; asymmetry; chemotaxis; polarity; protein localization