Definition and cellular localization

TMEM110, also designated as ''STIMATE'' (for STIM-activating enhancer), is an ER-resident multi-transmembrane protein identified through a proteomic study on the ER-PM junctions. The ER-PM junctions are defined as specialized junctional sites, also known as membrane contact sites, that connect the endoplasmic reticulum (ER) and the plasma membrane (PM), and are closely implicated in controlling lipid and calcium homeostasis in mammalian cells.

Function

TMEM110 is a positive modulator of calcium flux mediated by the STIM-ORAI signaling in vertebrates. STIMATE can physically associate with

STIM1 Stromal interaction molecule 1 is a protein that in humans is encoded by the ''STIM1'' gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane. Even though the pro ...

to promote conformational switch of STIM1 from inactive toward an activated state, thereby coupling to and gating the

ORAI Orai is a city in Uttar Pradesh, India. It is the administrative headquarters of Jalaun District. All administrative offices of Jalaun District, including the District Collectorate, police, telecom and various other government organizations are ...

calcium channels on the plasma membrane. Depletion of TMEM110 with

RNAi RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...

knockdown or

Cas9 Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic e ...

-mediated gene disruption substantially reduces the puncta formation of STIM1 at ER-PM junctions and remarkably inhibits the calcium/

calcineurin Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be bloc ...

NFAT Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the developme ...

signaling axis. More genetic and biochemical studies are needed to uncover more uncharted functions of this ER-resident protein at ER-PM junctions.

References

{{Reflist Proteins