{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in Drosophila revealed that a member of the Lgd protein family – whose function we refer to here as ZNF475 – is critical for preventing aberrant Notch activation during development. In these cells, the protein ensures the proper endosomal trafficking of the Notch receptor so that ligand‐independent activation is avoided; loss of its function leads to misrouting of Notch into an aberrant endosomal compartment and ectopic signaling. This fundamental role in maintaining signaling fidelity underscores the protein’s importance in developmental processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn mammalian systems, orthologs within the same conserved family – namely CC2D1A and CC2D1B – perform related functions. CC2D1A, for instance, localizes to endosomal membranes where it interacts with ESCRT-III components (such as CHMP4B) to ensure proper endosomal morphogenesis and regulate the trafficking of membrane proteins. Although CC2D1A is not universally required for all Notch signaling outputs, its activity is essential for maintaining appropriate endosomal size and dynamics, as evidenced by enlarged endosomes in its absence. Furthermore, the ability of CC2D1A and CC2D1B to rescue Drosophila Lgd mutants underscores the functional conservation across species."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in intracellular trafficking, a family member known as Freud-2/CC2D1B has been identified as a transcriptional repressor. This protein binds specifically to a dual repressor element (DRE) in the promoter region of the 5-HT1A receptor gene, thereby modulating its expression in both neuronal and non-neuronal cells. Knockdown studies demonstrate that loss of Freud-2/CC2D1B alleviates repression at this promoter, resulting in increased receptor expression, which highlights its importance in the fine-tuning of serotonergic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert Jaekel, Thomas Klein "}, {"type": "b", "children": [{"type": "t", "text": "The Drosophila Notch inhibitor and tumor suppressor gene lethal (2) giant discs encodes a conserved regulator of endosomal trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2006.09.019"}], "href": "https://doi.org/10.1016/j.devcel.2006.09.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17084358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17084358"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nadja Drusenheimer, Bernhard Migdal, Sandra Jäckel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Mammalian Orthologs of Drosophila Lgd, CC2D1A and CC2D1B, Function in the Endocytic Pathway, but Their Individual Loss of Function Does Not Affect Notch Signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1005749"}], "href": "https://doi.org/10.1371/journal.pgen.1005749"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26720614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26720614"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mahmoud R Hadjighassem, Kimberly Galaraga, Paul R Albert "}, {"type": "b", "children": [{"type": "t", "text": "Freud-2/CC2D1B mediates dual repression of the serotonin-1A receptor gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1460-9568.2010.07498.x"}], "href": "https://doi.org/10.1111/j.1460-9568.2010.07498.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21155902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21155902"}]}]}]}