title: POPX2 phosphatase regulates cell polarity and centrosome placement.
abstract: Proper centrosome positioning is critical for many cellular functions, such as cell migration and maintenance of polarity. During wound healing, fibroblasts orient their centrosomes such that they face the wound edge. The centrosome orientation determines the direction of cells' migration so that they can close the wound effectively. In this study, we investigated the regulation of centrosome polarization and have identified the phosphatase POPX2 as an important regulator of centrosome orientation. We found that POPX2 inhibits centrosome centration, but not rearward nuclear movement, by regulating multiple proteins that function in centrosome positioning. High POPX2 levels result in reduced motility of the kinesin-2 motor, which, in turn, inhibits the transport of N-cadherin to the cell periphery and cell junctions. Loss of N-cadherin localization to the cell membrane affects the localization of focal adhesions and perturbs CDC42-Par6/PKCζ signaling. In addition, overexpression of POPX2 also results in a loss of Par3 localization to the cell periphery and reduced levels of LIC2 (dynein light intermediate chain 2), leading to defects in microtubule tethering and dynamics at cell-cell contacts. Therefore, POPX2 functions as a regulator of signaling pathways to modulate the positioning of centrosome in fibroblast during wound healing.
authors.affiliation: a School of Biological Sciences; Nanyang Technological University; Singapore.
authors.forename: Jing-Ling
authors.initials: JL
authors.lastname: Hoon
authors.forename: Hoi-Yeung
authors.initials: HY
authors.lastname: Li
authors.forename: Cheng-Gee
authors.initials: CG
authors.lastname: Koh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D022101:Microtubule-Organizing Center / Q000378:metabolism; D041681:NIH 3T3 Cells; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C490202:Kif3a protein, mouse; C115084:Pard3 protein, mouse; C000600234:PPM1F protein, mouse; D010749:Phosphoprotein Phosphatases; D016547:Kinesins; D020764:cdc42 GTP-Binding Protein
keywords: Kinesin-2 motor; N-cadherin; POPX2 phosphatase; Par3; calcium/calmodulin kinase; centrosome; dynein light intermediate chain 2