{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DENN domain proteins comprise a family of guanine nucleotide exchange factors (GEFs) that activate Rab GTPases and thereby govern diverse steps of intracellular membrane trafficking. Although none of the supplied abstracts mention DENND10 explicitly by name, several reports in this collection describe the functions of DENN‐domain proteins in pathways that are likely to be shared by DENND10. For example, one study showed that a DENN‐domain GEF (FAM116A) acts with Rab14 to control the trafficking of ADAM10, thereby regulating cell–cell junction dynamics and promoting cell migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In another investigation, the non‐classical DENN domain protein FAM45A was found to localize predominantly to late endosomal compartments where it modulates endosome positioning, maturation, and exosome secretion through its nucleotide‐dependent interactions with Rab27a/b"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "; notably, FAM45A was also identified as a mercury‐binding protein in fish tissues, underscoring the multifaceted roles of DENN proteins in cellular physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, a separate report re‐annotated the neurodegeneration‐associated gene C9ORF72 as DENN‐like 72 (DENNL72), proposing that it, too, regulates membrane traffic via Rab switches, with implications for frontotemporal dementia and amyotrophic lateral sclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that DENN-domain proteins—including proteins presumed to share similar mechanisms with DENND10—act as key regulators of Rab GTPases to coordinate vesicle formation, endosomal maturation, and cargo recycling. In this context, DENND10 is inferred to function analogously by facilitating the exchange of GDP for GTP on specific Rab proteins, thereby contributing to processes as varied as cell polarization and migration, endosome dynamics, and possibly even aspects of cellular stress responses.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrea Linford, Shin-ichiro Yoshimura, Ricardo Nunes Bastos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2012.04.010"}], "href": "https://doi.org/10.1016/j.devcel.2012.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22595670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22595670"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jianjian Zhang, Kangning Zhang, Lijuan Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2019.02.006"}], "href": "https://doi.org/10.1016/j.bbamcr.2019.02.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30771381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30771381"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Bruna Cavecci-Mendonça, José Cavalcante de Souza Vieira, Paula Monteiro de Lima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Study of proteins with mercury in fish from the Amazon region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Food Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.foodchem.2019.125460"}], "href": "https://doi.org/10.1016/j.foodchem.2019.125460"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31732251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31732251"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Timothy P Levine, Rachel D Daniels, Alberto T Gatta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioinformatics (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/bioinformatics/bts725"}], "href": "https://doi.org/10.1093/bioinformatics/bts725"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23329412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23329412"}]}]}]}