title: Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y6 Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia.
abstract: Microglia clean up dead cells and debris through phagocytosis in the central nervous system. UDP-activated P2Y6 receptors (P2Y6Rs) induce the formation of phagocytic cup-like structure and P2Y6R expression is increased during the phagocytosis. However, it remains unclear how surface expression of P2Y6R is increased. PICK1 (protein interacting with C-kinase-1) interacts with various neurotransmitter receptors, transporters, and enzymes. We here report that PICK1 might interact with P2Y6R. Surface P2Y6R was reduced in microglia from PICK1-knockout mice and PICK1-knockdown BV2 cells, which was also confirmed by electrophysiological recordings, showing that P2Y6R-mediated current was increased by PICK1 overexpression but was reduced by PICK1-knockdown in BV2 microglia. Finally, PICK1 was sufficient to affect cytoskeletal aggregation and phagocytosis both in primary microglia and BV2 cells. These results indicate that PICK1 is an important regulator of P2Y6R expression and microglial phagocytosis.
authors.affiliation: Department of Microbiology and Immunology, Jiaxing University School of Medicine, Jiaxing, China. zhujia0322@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Blood Transfusion, Institute of Molecular Medicine, Zhejiang Provincial People's Hospital, 310014, Hangzhou, China.|Department of Neurobiology, Zhejiang University School of Medicine, 310058, Hangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, 750004, Yinchuan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, 750004, Yinchuan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Microbiology and Immunology, Jiaxing University School of Medicine, Jiaxing, China.
authors.forename: Shui-Lin
authors.initials: SL
authors.lastname: Xu
authors.affiliation: Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, 750004, Yinchuan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Zhejiang University School of Medicine, 310058, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, 750004, Yinchuan, China. 976153438@qq.com.
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D058105:Polymerization; D018048:Receptors, Purinergic P2 / Q000378:metabolism*
chemical_list: D000199:Actins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6
keywords: BV2; Microglia; P2Y6 receptor; PICK1