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• W3121490172 abstract "Abstract Lysosome-related organelles (LROs) are a category of secretory organelles enriched with ions such as calcium, which are maintained by ion transporters or channels. Homeostasis of these ions is important for LRO biogenesis and secretion. Hermansky-Pudlak syndrome (HPS) is a recessive disorder with defects in multiple LROs, typically platelet dense granules (DGs) and melanosomes. However, the underlying mechanism of DG deficiency is largely unknown. Using quantitative proteomics, we identified a previously unreported platelet zinc transporter, transmembrane protein 163 (TMEM163), which was significantly reduced in BLOC-1 (Dtnbp1sdy and Pldnpa)–, BLOC-2 (Hps6ru)–, or AP-3 (Ap3b1pe)–deficient mice and HPS patients (HPS2, HPS3, HPS5, HPS6, or HPS9). We observed similar platelet DG defects and higher intracellular zinc accumulation in platelets of mice deficient in either TMEM163 or dysbindin (a BLOC-1 subunit). In addition, we discovered that BLOC-1 was required for the trafficking of TMEM163 to perinuclear DG and late endosome marker–positive compartments (likely DG precursors) in MEG-01 cells. Our results suggest that TMEM163 is critical for DG biogenesis and that BLOC-1 is required for the trafficking of TMEM163 to putative DG precursors. These new findings suggest that loss of TMEM163 function results in disruption of intracellular zinc homeostasis and provide insights into the pathogenesis of HPS or platelet storage pool deficiency." @default.
• W3121490172 created "2021-02-01" @default.
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• W3121490172 date "2021-04-01" @default.
• W3121490172 modified "2023-10-14" @default.
• W3121490172 title "A zinc transporter, transmembrane protein 163, is critical for the biogenesis of platelet dense granules" @default.
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• W3121490172 doi "https://doi.org/10.1182/blood.2020007389" @default.
• W3121490172 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8020268" @default.
• W3121490172 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33513603" @default.
• W3121490172 hasPublicationYear "2021" @default.
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