Skip to Content
Merck
  • NKD2 mediates stimulation-dependent ORAI1 trafficking to augment Ca2+ entry in T cells.

NKD2 mediates stimulation-dependent ORAI1 trafficking to augment Ca2+ entry in T cells.

Cell reports (2021-08-26)
Beibei Wu, Jin Seok Woo, Pamela Vila, Marcus Jew, Jennifer Leung, Zuoming Sun, Sonal Srikanth, Yousang Gwack
ABSTRACT

Sustained activation of the Ca2+-release-activated Ca2+ (CRAC) channel is pivotal for effector T cell responses. The mechanisms underlying this sustainability remain poorly understood. We find that plasma membrane localization of ORAI1, the pore subunit of CRAC channels, is limited in effector T cells, with a significant fraction trapped in intracellular vesicles. From a targeted screen, we identify an essential component of ORAI1+ vesicles, naked cuticle homolog 2 (NKD2). Mechanistically, NKD2, an adaptor molecule activated by signaling pathways downstream of T cell receptors, orchestrates trafficking and insertion of ORAI1+ vesicles to the plasma membrane. Together, our findings suggest that T cell receptor (TCR)-stimulation-dependent insertion of ORAI1 into the plasma membrane is essential for sustained Ca2+ signaling and cytokine production in T cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Polybrene Infection / Transfection Reagent, A highly efficient method of gene transfer into mammalian cells leveraging infection with retroviral vectors.
SKU
Pack Size
Availability
Price
Quantity
Millipore
Ionomycin, Free Acid, Streptomyces conglobatus in Solution
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Anti-Orai1 Antibody, Intracellular, Chemicon®, from rabbit
SKU
Pack Size
Availability
Price
Quantity