Mechanistic view on domains mediating STIM1-Orai coupling

作者：Fahmer Marc; Muik Martin; Derler Isabella; Schindl Rainer; Fritsch Reinhard; Frischauf Irene; Romanin Christoph^*

来源：Immunological Reviews, 2009, 231(1): 99-112.

DOI：10.1111/j.1600-065x.2009.00815.x

• signal transduction
• signaling proteins
• immunodeficiency diseases
• mast cells
• T cells

Calcium (Ca<SU2 </SU) entry into non-excitable cells is mainly carried by store-operated channels, which serve essential functions ranging from regulation of transcription to cell growth. The best-characterized store-operated current, initially discovered in T lymphocytes and mast cells, is the Ca<SU2 </SU release-activated Ca<SU2 </SU (CRAC) current. The search for the molecular components of the CRAC channel has recently identified stromal interaction molecule 1 (STIM1) as the Ca<SU2 </SU sensor in the endoplasmic reticulum (ER) and Orai1 as the CRAC channel pore. ER store depletion results in formation of STIM1 puncta that trigger Ca<SU2 </SU influx via Orai1 channels. This review covers the role of domains within STIM1 and Orai and enlightens their function in the STIM1/Orai coupling process. Moreover, a molecular interpretation focuses on interactions between cytosolic portions of STIM1 and Orai together with a mechanistic view on the loss of function of the SCID (severe combined immunodeficiency)-linked Orai1 R91W mutant channel. The architecture of the selectivity filter of Orai channels is finally elucidated based on permeation properties of Orai pore mutants.

• 出版日期2009-9