{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HHATL (Hedgehog acyltransferase‐like) is a member of the membrane‐bound O‐acyltransferase (MBOAT) family that has emerged as an important regulator of Hedgehog signaling and extracellular matrix homeostasis. In vertebrate systems, HHATL is highly expressed in cardiac and muscle tissues, where it appears to modulate the secretion of Hedgehog ligands and thereby influence morphogenesis, differentiation, and cell–cell communication. For example, studies in zebrafish have shown that reduced expression of HHATL leads to cardiac defects and the upregulation of hypertrophic markers—a process mediated in part by calcineurin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, proteomic profiling in rat myocardial tissue from epileptic models has identified HHATL as a key protein associated with cardiac injury, suggesting that its dysregulation may contribute to pathological remodeling under stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In yeast, the homologous protein Gup1 has been implicated in a broad array of functions that include lipid remodeling, maintenance of membrane and cell wall integrity, proper assembly of GPI anchors, and the organization of the extracellular matrix."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Although a classical Hedgehog signaling pathway is not present in yeast, these observations suggest that the evolutionarily conserved activities of HHATL/Gup1 are linked to lipid modification processes that are critical for morphogenesis and cell integrity.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies support a model in which HHATL functions to regulate the posttranslational lipid modification of proteins—thereby modulating Hedgehog ligand secretion—and participates in maintaining extracellular matrix structure and cellular integrity. Disruption of HHATL expression is associated with cardiac hypertrophy and myocardial injury in vertebrates and, in yeast, parallels defects in colony morphology and membrane dynamics. This conserved role in modulating signal transduction and membrane remodeling positions HHATL as an important factor in both normal developmental processes and disease‐associated tissue remodeling.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xingjuan Shi, Yu Zhang, Yijie Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zebrafish hhatla is involved in cardiac hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.30106"}], "href": "https://doi.org/10.1002/jcp.30106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33052609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33052609"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Peng Zhang, Li Zhang, Yongguo Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative Proteomic Analysis To Identify Differentially Expressed Proteins in Myocardium of Epilepsy Using iTRAQ Coupled with Nano-LC-MS/MS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.jproteome.7b00579"}], "href": "https://doi.org/10.1021/acs.jproteome.7b00579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29090925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29090925"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Joana Tulha, Cândida Lucas "}, {"type": "b", "children": [{"type": "t", "text": "Saccharomyces cerevisiae mitochondrial Por1/yVDAC1 (voltage-dependent anion channel 1) interacts physically with the MBOAT O-acyltransferase Gup1/HHATL in the control of cell wall integrity and programmed cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEMS Yeast Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/femsyr/foy097"}], "href": "https://doi.org/10.1093/femsyr/foy097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30184078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30184078"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fábio Faria-Oliveira, Joana Carvalho, Célia Ferreira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative differential proteomics of yeast extracellular matrix: there is more to it than meets the eye."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Microbiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12866-015-0550-1"}], "href": "https://doi.org/10.1186/s12866-015-0550-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26608260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26608260"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Célia Ferreira, Sónia Silva, Fábio Faria-Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Candida albicans virulence and drug-resistance requires the O-acyltransferase Gup1p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Microbiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2180-10-238"}], "href": "https://doi.org/10.1186/1471-2180-10-238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20843317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20843317"}]}]}]}