title: A novel role for 14-kDa phosphohistidine phosphatase in lamellipodia formation.
abstract: Cell migration involves dynamic regulation of the actin cytoskeleton, which exhibits rapid actin polymerization at the leading edge of migrating cells. This process relies on regulated recruitment of actin nucleators and actin-binding proteins to the leading edge to polymerize new actin filaments. Many of these proteins have been identified, including the actin-related protein (Arp) 2/3 complex, which has emerged as the core player in the initiation of actin polymerization. However, the functional coordination of these proteins is unclear. Previously, we have demonstrated that the 14-kDa phosphohistidine phosphatase (PHP14) is involved in cell migration regulation and affects actin cytoskeleton reorganization. Here, we show that PHP14 may regulate actin remodeling directly and play an important role in dynamic regulation of the actin cytoskeleton. We observed a colocalization of PHP14 with Arp3 and F-actin at the leading edge of migrating cells. Moreover, PHP14 was recruited to the actin remodeling sites in parallel with Arp3 during lamellipodia formation. Furthermore, PHP14 knockdown impaired Arp3 localization at the leading edge of lamellipodia, as well as lamellipodia formation. Most importantly, we found that PHP14 was a novel F-actin-binding protein, displaying an Arp2/3-dependent localization to the leading edge. Collectively, our results indicated a crucial role for PHP14 in the dynamic regulation of the actin cytoskeleton and cell migration.
authors.affiliation: a Experimental Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.|b National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Anjian
authors.initials: A
authors.lastname: Xu
authors.affiliation: a Experimental Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.|b National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Li
authors.affiliation: a Experimental Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Siwen
authors.initials: S
authors.lastname: Li
authors.affiliation: c Department of Pathology , Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.affiliation: d Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Shanna
authors.initials: S
authors.lastname: Wu
authors.affiliation: a Experimental Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.|b National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Experimental Center, Beijing Friendship Hospital, Capital Medical University , Beijing , China.|b National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D006367:HeLa Cells; D006639:Histidine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D000199:Actins; D006639:Histidine; D010744:Phosphoric Monoester Hydrolases; C005436:phosphohistidine
keywords: Arp3; F-actin; PHP14; cell migration; leading edge