{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRPC7, a member of the canonical transient receptor potential (TRPC) family, plays a central role in calcium‐signaling pathways activated by phospholipase C (PLC). Cloned from human brain, hTRP7 was shown to mediate store‐operated calcium entry upon depletion of intracellular calcium stores (1). In HEK‐293 cells, expression studies indicate that TRPC7 can be preferentially activated by PLC‐coupled receptor stimulation rather than by store depletion under transient expression conditions (2), whereas in other models TRPC7 forms heteromeric complexes with TRPC1 and TRPC3 that are essential for store-operated calcium influx (3) and for receptor-operated calcium entry in lymphocytes (4).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn native cells such as keratinocytes, TRPC7 contributes to receptor-operated calcium entry in response to muscarinic, purinergic, and diacylglycerol (DAG) mimetics, underscoring its importance in receptor-initiated signaling (5). TRPC7 is directly activated by DAG and exhibits characteristics such as constitutive activity and negative regulation by extracellular Ca²⁺ (6). In kidney epithelial cells, mutant forms of TRPP2 associate with TRPC7 to enhance receptor-stimulated Ca²⁺ influx and alter the ion-permeating properties of the channel (7). In addition, TRPC7 is subject to rapid modulation by phosphorylation; for example, cGMP-dependent protein kinase I phosphorylates TRPC7 at threonine 15 to suppress receptor-mediated Ca²⁺ entry and downstream CREB phosphorylation, while dynamic changes in PI(4,5)P₂ levels following PLC activation further fine-tune channel inactivation (8, 9).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in basal Ca²⁺ homeostasis and receptor signaling, TRPC7 has important pathophysiological implications. In the skin, TRPC7 functions as a nociceptive mechanoreceptor that mediates ultraviolet B (UVB)-induced Ca²⁺ influx and subsequent production of reactive oxygen species, processes that initiate premature skin aging and tumorigenesis (10). Collectively, these findings reveal that TRPC7 is a multifaceted Ca²⁺ channel whose activation and regulation—dependent on cell type, expression context, and interaction with other proteins—are critical for normal cellular physiology as well as for the development of certain disease states."}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "."}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "."}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Antonio Riccio, Cesar Mattei, Rosemary E Kelsell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112313200"}], "href": "https://doi.org/10.1074/jbc.M112313200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11805119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11805119"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jean-Philippe Lièvremont, Gary St J Bird, James W Putney "}, {"type": "b", "children": [{"type": "t", "text": "Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00350.2004"}], "href": "https://doi.org/10.1152/ajpcell.00350.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15342342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15342342"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tatiana K Zagranichnaya, Xiaoyan Wu, Mitchel L Villereal "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M505842200"}], "href": "https://doi.org/10.1074/jbc.M505842200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15972814"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15972814"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jean-Philippe Lievremont, Takuro Numaga, Guillermo Vazquez, et al. 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