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

First Author  Matza D Year  2008
Journal  Immunity Volume  28
Issue  1 Pages  64-74
PubMed ID  18191595 Mgi Jnum  J:131148
Mgi Id  MGI:3773083 Doi  10.1016/j.immuni.2007.11.020
Citation  Matza D, et al. (2008) A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation. Immunity 28(1):64-74
abstractText  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.
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