A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation.
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.
Matza
Didi
D
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Badou
Abdallah
A
Kobayashi
Koichi S
KS
Goldsmith-Pestana
Karen
K
Masuda
Yutaka
Y
Komuro
Akihiko
A
McMahon-Pratt
Diane
D
Marchesi
Vincent T
VT
Flavell
Richard A
RA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020013:Calcium Signaling / Q000276:immunology*; D051242:Caveolin 1 / Q000378:metabolism; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D007896:Leishmaniasis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C489572:Ahnak protein, mouse; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D008565:Membrane Proteins; D009363:Neoplasm Proteins