Referenced in: none

Automatically associated channels: Cav1.1

Title: A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation.

Authors: Didi Matza, Abdallah Badou, Koichi S Kobayashi, Karen Goldsmith-Pestana, Yutaka Masuda, Akihiko Komuro, Diane McMahon-Pratt, Vincent T Marchesi, Richard A Flavell

Journal, date & volume: Immunity, 2008 Jan , 28, 64-74

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18191595

Abstract
Engagement of the T cell antigen receptor (TCR) during antigen presentation initiates a coordinated action of a large number of signaling proteins and ion channels. AHNAK1 is a scaffold protein, highly expressed by CD4+ T cells, and is a critical component for calcium signaling. We showed that AHNAK1-deficient mice were highly susceptible to Leishmania major infection. AHNAK1-deficient CD4+ T cells responded poorly to TCR stimulation in vitro with low proliferation and low Interleukin-2 production. Furthermore, AHNAK1 deficiency resulted in a reduced calcium influx upon TCR crosslinking and subsequent poor activation of the transcription factor NFAT. AHNAK1 was required for plasma membrane expression of L-type calcium channels alpha 1S (Cav1.1), probably through its interaction with the beta regulatory subunit. Thus, AHNAK1 plays an essential role in T cell Ca2+ signaling through Cav1 channels, triggered via TCR activation; therefore, AHNAK1 is a potential target for therapeutic intervention.