CRAC channels and STIM1 are absolutely vital to activating the immune system.
To determine that STIM1 is responsible for selectivity and opening, the researchers created a mutated CRAC channel designed to keep the pore open without the assistance of STIM1.
When STIM1 was added back in, the channel became very selective for calcium ions again, like the normal channel.
Even at low doses of STIM1, the unmutated channel lost its normally high calcium selectivity, allowing the entry of multiple types of ions.
Here we show that STIM1 senses temperature and has a profound impact on immune cells," said the study's principal investigator, Scripps Research professor Ardem Patapoutian.
The research team, which included Bertrand Coste and Jayanti Mathur, also of the Patapoutian lab, found that STIM1 could be activated by heat with a high degree of temperature sensitivity.
Both STIM1 and a plasma membrane pore-forming protein known as Orai1 have recently been identified as essential components of the so-called the calcium release activated calcium (CRAC) channel.
We have identified a direct association of TRPC1 with caveolar microdomains, Cav1 and STIM1 respectively.
CONCLUSION: In conclusion, we propose that the association of TRPC1 with Cav1 is required for targeting the channel to specific PM compartments however, following ER store-depletion, the dissociation of the caveolae-associated 'TRPC1-Cav1' complex by STIM1 is imperative for the activation of SOCE and cell proliferation.
STIM1, an essential and conserved component of store- operated Ca2+ channel function (2005).
2008) Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE).
In mice SMG, TRPC1 and STIM1
associate with caveolar rafts as opposed to their non-raft partitioning in cav1-/- tissue.