Caveolin-1 forms a complex with P2X7 receptor and tunes P2X7-mediated ATP signaling in mouse bone marrow-derived macrophages

Author:

Sawai Yuuki1,Suzuki Yoshiaki1ORCID,Asagiri Masataka2,Hida Shigeaki3,Kondo Rubii1,Zamponi Gerald W.45,Giles Wayne R.4,Imaizumi Yuji1ORCID,Yamamura Hisao1ORCID

Affiliation:

1. Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

2. Department of Pharmacology, Yamaguchi University Graduate School of Medicine, Ube, Japan

3. Department of Molecular and Cellular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

4. Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

5. Department of Clinical Neurosciences, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

Abstract

In bone marrow-derived macrophages, Cav-1 suppresses the macropore formation of P2X7 receptors through their direct or indirect interactions, resulting in reduced membrane permeability of cations (Ca2+ and K+) and large cell-impermeable dye (TO-PRO3) induced by ATP. Cav-1 also inhibits ATP-induced IL-1β secretion, ROS production, GSDMD cleavage, and pyroptosis. Cav-1 contributes to the maintenance of proper immune responses by finely tuning IL-1β secretion and cell death in macrophages.

Funder

MEXT | Japan Society for the Promotion of Science

Suzuken Memorial Foundation

Takeda Science Foundation

Pharmacological Research Foundation

Canada Research Chairs

Japan Foundation for Applied Enzymology

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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