Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC3

Title: Impairment of survival signaling and efferocytosis in TRPC3-deficient macrophages.

Authors: Jean-Yves Tano, Kathryn Smedlund, Robert Lee, Joel Abramowitz, Lutz Birnbaumer, Guillermo Vazquez

Journal, date & volume: Biochem. Biophys. Res. Commun., 2011 Jul 8 , 410, 643-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21684255

Abstract
We have recently shown that in macrophages proper operation of the survival pathways phosphatidylinositol-3-kinase (PI3K)/AKT and nuclear factor kappa B (NFkB) has an obligatory requirement for constitutive, non-regulated Ca(2+) influx. In the present work we examined if Transient Receptor Potential Canonical 3 (TRPC3), a member of the TRPC family of Ca(2+)-permeable cation channels, contributes to the constitutive Ca(2+) influx that supports macrophage survival. We used bone marrow-derived macrophages obtained from TRPC3(-/-) mice to determine the activation status of survival signaling pathways, apoptosis and their efferocytic properties. Treatment of TRPC3(+/+) macrophages with the pro-apoptotic cytokine TNFα induced time-dependent phosphorylation of IκBα, AKT and BAD, and this was drastically reduced in TRPC3(-/-) macrophages. Compared to TRPC3(+/+) cells TRPC3(-/-) macrophages exhibited reduced constitutive cation influx, increased apoptosis and impaired efferocytosis. The present findings suggest that macrophage TRPC3, presumably through its constitutive function, contributes to survival signaling and efferocytic properties.