A Scaffold Protein, AHNAK1, Is Required for Calcium Signaling during T Cell Activation

• Published in: Immunity (Cambridge, Mass.) Vol. 28; no. 1; pp. 64 - 74
• Main Authors: Matza, Didi, Badou, Abdallah, Kobayashi, Koichi S., Goldsmith-Pestana, Karen, Masuda, Yutaka, Komuro, Akihiko, McMahon-Pratt, Diane, Marchesi, Vincent T., Flavell, Richard A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2008; Elsevier Limited
• Subjects: Animals; Calcium; Calcium Signaling - immunology; Caveolin 1 - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - microbiology; Cell Proliferation; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Kinases; Leishmania major; Leishmaniasis - immunology; Lymphocyte Activation - immunology; Medical research; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Mice, Transgenic; MOLIMMUNO; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Neoplasm Proteins - metabolism; Parasites; Reverse Transcriptase Polymerase Chain Reaction; Rodents; MOLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2007.11.020

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 α1S (Ca
v1.1), probably through its interaction with the β regulatory subunit. Thus, AHNAK1 plays an essential role in T cell Ca
2+ signaling through Ca
v1 channels, triggered via TCR activation; therefore, AHNAK1 is a potential target for therapeutic intervention.