Abstract
Ca 2+ influx via store-operated Ca 2+ release activated Ca 2+ (CRAC) channels represents a main signaling pathway for T-cell activation as well as mast-cell degranulation. The ER-located Ca 2+-sensor, STIM1 and the Ca 2+-selective ion pore, Orai1 in the membrane are sufficient to fully reconstitute CRAC currents. Their identification, but even more the recent structural resolution of both proteins by X-ray crystallography has substantially advanced the understanding of the activation mechanism of CRAC channels. In this review, we provide a detailed description of the STIM1/Orai1 signaling pathway thereby focusing on the critical domains mediating both, intra- as well as intermolecular interactions and on the ion permeation pathway. Based on the results of functional studies as well as the recently published crystal structures, we portray a mechanistic view of the steps in the CRAC channel signaling cascade ranging from STIM1 oligomerization over STIM1-Orai1 coupling to the ultimate Orai1 channel activation and permeation
| Original language | English |
|---|---|
| Pages (from-to) | 330-343 |
| Number of pages | 13 |
| Journal | Channels |
| Volume | 7 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sept 2013 |
Fields of science
- 103036 Theoretical physics
- 211904 Biomechanics
- 103020 Surface physics
- 210 Nanotechnology
- 104010 Macromolecular chemistry
- 106006 Biophysics
- 106022 Microbiology
- 106048 Animal physiology
- 209 Industrial Biotechnology
- 304 Medical Biotechnology
- 404 Agricultural Biotechnology, Food Biotechnology
- 106049 Ultrastructure research
- 103021 Optics
- 106002 Biochemistry
- 104017 Physical chemistry
- 208 Environmental Biotechnology
- 104014 Surface chemistry
- 106023 Molecular biology
- 107 Other Natural Sciences
- 301110 Physiology
- 301206 Pharmacology
- 206 Medical Engineering
- 301306 Medical molecular biology
- 302044 Medical physics
- 301902 Immunology
- 305910 Traffic medicine
JKU Focus areas
- Engineering and Natural Sciences (in general)