UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis

Schuichi Koizumi, Yukari Shigemoto-Mogami, Kaoru Nasu-Tada, Yoichi Shinozaki, Keiko Ohsawa, Makoto Tsuda, Bhalchandra V. Joshi, Kenneth A. Jacobson, Shinichi Kohsaka and Kazuhide Inoue ()
Additional contact information
Schuichi Koizumi: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
Yukari Shigemoto-Mogami: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
Kaoru Nasu-Tada: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
Yoichi Shinozaki: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan
Keiko Ohsawa: National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan
Makoto Tsuda: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka 812-8582, Japan
Bhalchandra V. Joshi: Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
Kenneth A. Jacobson: Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA
Shinichi Kohsaka: National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan
Kazuhide Inoue: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka 812-8582, Japan

Nature, 2007, vol. 446, issue 7139, 1091-1095

Abstract: Keeping things tidy Phagocytosis is thought to be initiated by activation of phagocytosis-promoting receptors that recognize 'eat-me' signals such as phosphatidylserine or amyloid-β expressed in the apoptotic cells. But now Koizumi et al. demonstrate a novel type of microglial phagocytosis that requires neither typical 'eat-me' signals nor Fc receptor ligands for initiation. Instead, this phagocytosis is promoted by the diffusible extracellular molecule uridine 5′-diphosphate, released by injured cells. The UDP activates P2Y6 receptors on the microglial surface. The clearance of dead cells is crucial to the maintenance of brain function, so these findings may have implications for a range of central nervous system diseases.

Date: 2007
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DOI: 10.1038/nature05704

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