Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y6 Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia

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• 作者：Jia Zhu ; Zhen Wang ; Nan Zhang ; Jiao Ma ; Shui-Lin Xu ; Yin Wang…
• 关键词：PICK1 ; P2Y6 receptor ; BV2 ; Microglia
• 刊名：Neurochemical Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：41
• 期：4
• 页码：795-803
• 全文大小：4,799 KB
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• 作者单位：Jia Zhu (1)
  Zhen Wang (2) (4)
  Nan Zhang (3)
  Jiao Ma (3)
  Shui-Lin Xu (1)
  Yin Wang (3)
  Ying Shen (4)
  Yun-Hong Li (3)
  
  1. Department of Microbiology and Immunology, Jiaxing University School of Medicine, Jiaxing, China
  2. Department of Blood Transfusion, Institute of Molecular Medicine, Zhejiang Provincial People’s Hospital, 310014, Hangzhou, China
  4. Department of Neurobiology, Zhejiang University School of Medicine, 310058, Hangzhou, China
  3. Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, 750004, Yinchuan, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Biochemistry
  Neurology
  
• 出版者：Springer Netherlands
• ISSN：1573-6903

文摘

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.