{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTIMATE, encoded by TMEM110, is an endoplasmic reticulum (ER)–resident multi-transmembrane protein that functions at specialized ER–plasma membrane (PM) junctions to enhance store-operated Ca²⁺ entry. It achieves this by physically interacting with the Ca²⁺ sensor STIM1 and facilitating a conformational switch that promotes STIM1 clustering (puncta formation) at ER–PM junctions. This clustering is essential for the coupling of STIM1 with ORAI1, which in turn triggers downstream Ca²⁺ influx and activation of Ca²⁺‐dependent signaling pathways including NFAT activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in promoting STIM1 activation, STIMATE is also crucial for the structural organization of ER–PM junctions. It regulates both the maintenance of these junctions over the long term and their rapid remodeling during the initiation of store-dependent Ca²⁺ signaling. Such dual functionality underscores STIMATE’s importance in ensuring that the spatial architecture necessary for effective STIM–ORAI signaling is preserved and dynamically adjusted in response to cellular stimuli."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these studies highlight STIMATE as a key positive regulator of Ca²⁺ influx. By modulating STIM1’s active conformation and maintaining the integrity and dynamic regulation of ER–PM junctions, STIMATE plays a pivotal role in orchestrating the spatial and temporal aspects of store-operated Ca²⁺ signaling, with significant implications for both normal physiology and pathophysiological states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ji Jing, Lian He, Aomin Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca²⁺ influx."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3234"}], "href": "https://doi.org/10.1038/ncb3234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26322679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26322679"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ariel Quintana, Vangipurapu Rajanikanth, Suzette Farber-Katz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1521924112"}], "href": "https://doi.org/10.1073/pnas.1521924112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26644574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26644574"}]}]}]}