| http://purl.uniprot.org/citations/34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34905616 | http://www.w3.org/2000/01/rdf-schema#comment | "Platelet α-granules regulate hemostasis and myriad other physiological processes, but their biogenesis is unclear. Mutations in only 3 proteins are known to cause α-granule defects and bleeding disorders in humans. Two such proteins, VPS16B and VPS33B, form a complex mediating transport of newly synthesized α-granule proteins through megakaryocyte (MK) endosomal compartments. It is unclear how the VPS16B/VPS33B complex accomplishes this function. Here we report VPS16B/VPS33B associates physically with Syntaxin 12 (Stx12), a SNARE protein that mediates vesicle fusion at endosomes. Importantly, Stx12-deficient MKs display reduced α-granule numbers and overall levels of α-granule proteins, thus revealing Stx12 as a new component of the α-granule biogenesis machinery. VPS16B/VPS33B also binds CCDC22, a component of the CCC complex working at endosome exit sites. CCDC22 competes with Stx12 for binding to VPS16B/VPS33B, suggesting a possible hand-off mechanism. Moreover, the major CCC form expressed in MKs contains COMMD3, one of 10 COMMD proteins. Deficiency of COMMD3/CCDC22 causes reduced α-granule numbers and overall levels of α-granule proteins, establishing the COMMD3/CCC complex as a new factor in α-granule biogenesis. Furthermore, P-selectin traffics through the cell surface in a COMMD3-dependent manner and depletion of COMMD3 results in lysosomal degradation of P-selectin and PF4. Stx12 and COMMD3/CCC deficiency cause less severe phenotypes than VPS16B/VPS33B deficiency, suggesting Stx12 and COMMD3/CCC assist but are less important than VPS16B/VPS33B in α-granule biogenesis. Mechanistically, our results suggest VPS16B/VPS33B coordinates the endosomal entry and exit of α-granule proteins by linking the fusogenic machinery with a ubiquitous endosomal retrieval complex that is repurposed in MKs to make α-granules."xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood.2021012056"xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/author | "Di Pietro S.M."xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/author | "Ambrosio A.L."xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/author | "Febvre H.P."xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/pages | "922-935"xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/title | "Syntaxin 12 and COMMD3 are new factors that function with VPS33B in the biogenesis of platelet alpha-granules."xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://purl.uniprot.org/core/volume | "139"xsd:string |
| http://purl.uniprot.org/citations/34905616 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34905616 |
| http://purl.uniprot.org/citations/34905616 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34905616 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z555-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z577-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z589-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_B7Z1N4-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_B7Z6M7-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_B0AZT9-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_B3KY73-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_B4DSZ1-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_F5H008-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_Q86Y82-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_Q6LEU0-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |
| http://purl.uniprot.org/uniprot/#_Q9H267-mappedCitation-34905616 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34905616 |