| http://purl.uniprot.org/citations/30892133 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30892133 | http://www.w3.org/2000/01/rdf-schema#comment | "Several lines of evidence support the occurrence of cross-regulation between the endocytic pathway and autophagy, but the molecular mechanisms regulating this process are not well-understood. Here, we show that the calcium sensor UNC13D regulates the molecular mechanism of late endosomal trafficking and endosomal maturation, and defects in UNC13D lead to macroautophagy upregulation. unc13d-null cells showed impaired endosomal trafficking and defective endocytic flux. The defective phenotypes were rescued by the expression of UNC13D but not by its STX7-binding-deficient mutant. This defective endosomal function in UNC13D-deficient cells resulted in increased autophagic flux, increased long-lived protein degradation, decreased SQSTM1/p62 protein levels and increased autolysosome formation as determined by biochemical, microscopy and structural methods. The autophagic phenotype was not associated with increased recruitment of the UNC13D-binding proteins and autophagy regulators, RAB11 or VAMP8, but was caused, at least in part, by TFEB-mediated upregulation of a subset of autophagic and lysosomal genes, including Atg9b. Downregulation of TFEB decreased Atg9b levels and decreased macroautophagy in unc13d-null cells. UNC13D upregulation corrected the defects in endolysosomal trafficking and decreased the number of accumulated autophagosomes in a cellular model of the lysosomal-storage disorder cystinosis, under both fed and starvation conditions, identifying UNC13D as an important new regulatory molecule of autophagy regulation in cells with lysosomal disorders. Abbreviations ACTB: actin, beta; CTSB: cathepsin B; EEA1: early endosome antigen 1; ESCRT: endosomal sorting complex required for transport; FHL3: familial hemophagocytic; lymphohistiocytosis type 3; HEX: hexosaminidase; HLH: hemophagocytic lymphohistiocytosis; LSD: lysosomal storage disorder; MEF: mouse embryonic fibroblast; SEM: standard errors of the mean; SNARE: soluble n-ethylmaleimide-sensitive-factor attachment receptor; STX: syntaxin; SYT7: synaptotagmin VII; TFE3: transcription factor E3; TFEB: transcription factor EB; TIRF: total internal reflection fluorescence ULK1: unc-51 like kinase 1; UNC13D: unc-13 homolog d; VAMP: vesicle-associate membrane protein; WT: wild-type."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.org/dc/terms/identifier | "doi:10.1080/15548627.2019.1596475"xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "He J."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "Johnson J.L."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "Napolitano G."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "Catz S.D."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "Ramadass M."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/author | "Rahman F."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/name | "Autophagy"xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/pages | "1738-1756"xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/title | "Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency."xsd:string |
| http://purl.uniprot.org/citations/30892133 | http://purl.uniprot.org/core/volume | "15"xsd:string |
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