Protein Interacting C-Kinase 1 Modulates Surface Expression of P2Y6 Purinoreceptor, Actin Polymerization and Phagocytosis in Microglia
- 397 Downloads
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.
KeywordsPICK1 P2Y6 receptor BV2 Microglia
Α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor
Ca2+-binding adapter molecule 1
Protein interacting with C-kinase 1
Protein kinase C
This work was supported by grants from National Natural Science Foundation of China (81501043, 31460257, 31471024, and 81571098).
Compliance with Ethical Standards
Conflict of interest
All authors declare that there are no conflicts of interest on the paper.
- 22.Nguyen TT, Kim YM, Kim TD, Le OT, Kim JJ, Kang HC, Hasegawa H, Kanaho Y, Jou I, Lee SY (2013) Phosphatidylinositol 4-phosphate 5-kinase α facilitates Toll-like receptor 4-mediated microglial inflammation through regulation of the Toll/interleukin-1 receptor domain-containing adaptor protein (TIRAP) location. J Biol Chem 288:5645–5659CrossRefPubMedPubMedCentralGoogle Scholar