{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GRAMD2A is a GRAM‐domain–containing protein that plays a central role in organizing specialized membrane contact sites between the endoplasmic reticulum (ER) and the plasma membrane (PM). Studies have demonstrated that GRAMD2A localizes to ER–PM contact sites where it co‐localizes with tether proteins such as E‐Syt2/3 in a phosphoinositide‐dependent manner. In these domains—particularly those enriched in PI(4,5)P2—GRAMD2A pre‐marks regions that are subsequently used for efficient recruitment of STIM1, thereby contributing to the regulation of calcium homeostasis and other pleiotropic functions at the ER–PM interface."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role as a structural organizer at contact sites, GRAMD2A (or its related family member designated GRAMD2) is subject to epigenetic regulation; for example, maternal preconception fatty acid levels have been associated with increased methylation at the GRAMD2 gene, suggesting that nutritional exposures may influence its expression and downstream cellular functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, GRAMD2 has been identified as a highly specific marker of alveolar epithelial type I (AT1) cells in the lung, underscoring its potential role in cell identity and offering a novel tool for isolating and studying these cells in the context of distal lung diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, GRAMD2A functions as an organizer of ER–PM membrane contact sites that are critical for calcium signaling and cellular homeostasis. Its regulation by nutritional factors and selective expression in specific cell types further highlights its diverse roles in cellular physiology.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marina Besprozvannaya, Eamonn Dickson, Hao Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.31019"}], "href": "https://doi.org/10.7554/eLife.31019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29469807"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29469807"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Paula Nunes, Nicolas Demaurex "}, {"type": "b", "children": [{"type": "t", "text": "GRAM marks the spot for STIM. Commentary on \"GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells\"."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Calcium (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ceca.2018.04.002"}], "href": "https://doi.org/10.1016/j.ceca.2018.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29684786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29684786"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sonia L Robinson, Sunni L Mumford, Weihua Guan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Maternal fatty acid concentrations and newborn DNA methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Clin Nutr (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ajcn/nqz311"}], "href": "https://doi.org/10.1093/ajcn/nqz311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31858113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31858113"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Crystal N Marconett, Beiyun Zhou, Mitsuhiro Sunohara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell-Specific Genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2016-0071OC"}], "href": "https://doi.org/10.1165/rcmb.2016-0071OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27749084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27749084"}]}]}]}