Identification and Characterization of the Interaction between VPS33B and SNAREs
VPS33B is a Sec1/Munc18 protein required for the biogenesis of α-granules in megakaryocytes, which give rise to platelets. Mutations in VPS33B cause arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Platelets from ARC patients completely lack α-granules, causing a bleeding disorder...
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ndltd-LACETR-oai-collectionscanada.gc.ca-OTU.1807-313942013-04-20T05:22:25ZIdentification and Characterization of the Interaction between VPS33B and SNAREsPuhacz, MichaelSNAREsSec1/Munc18VPS33Bsyntaxin-6megakaryocyteplatelet0379VPS33B is a Sec1/Munc18 protein required for the biogenesis of α-granules in megakaryocytes, which give rise to platelets. Mutations in VPS33B cause arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Platelets from ARC patients completely lack α-granules, causing a bleeding disorder. VPS33B plays a role in vesicular fusion events through its interaction with the SNARE proteins, though no such interactions have been identified. Here, it is shown that VPS33B interacts with STX6, a member of the syntaxin subfamily of SNAREs. The introduction of ARC mutations into VPS33B completely abrogated binding to STX6. Confocal microscopy studies revealed STX6 co-localizes well with markers of the α-granule biogenesis pathway. This implies a role for the interaction of VPS33B with STX6 in α-granule biogenesis. Based on the known structure of STX6 and that predicted of VPS33B, suggests a novel and unique mode of binding between VPS33B and STX6 compared to other identified SM-STX pairs.Kahr, Walter2011-112011-12-19T18:56:59ZNO_RESTRICTION2011-12-19T18:56:59Z2011-12-19Thesishttp://hdl.handle.net/1807/31394en_ca |
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SNAREs Sec1/Munc18 VPS33B syntaxin-6 megakaryocyte platelet 0379 |
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SNAREs Sec1/Munc18 VPS33B syntaxin-6 megakaryocyte platelet 0379 Puhacz, Michael Identification and Characterization of the Interaction between VPS33B and SNAREs |
description |
VPS33B is a Sec1/Munc18 protein required for the biogenesis of α-granules in megakaryocytes, which give rise to platelets. Mutations in VPS33B cause arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Platelets from ARC patients completely lack α-granules, causing a bleeding disorder. VPS33B plays a role in vesicular fusion events through its interaction with the SNARE proteins, though no such interactions have been identified. Here, it is shown that VPS33B interacts with STX6, a member of the syntaxin subfamily of SNAREs. The introduction of ARC mutations into VPS33B completely abrogated binding to STX6. Confocal microscopy studies revealed STX6 co-localizes well with markers of the α-granule biogenesis pathway. This implies a role for the interaction of VPS33B with STX6 in α-granule biogenesis. Based on the known structure of STX6 and that predicted of VPS33B, suggests a novel and unique mode of binding between VPS33B and STX6 compared to other identified SM-STX pairs. |
author2 |
Kahr, Walter |
author_facet |
Kahr, Walter Puhacz, Michael |
author |
Puhacz, Michael |
author_sort |
Puhacz, Michael |
title |
Identification and Characterization of the Interaction between VPS33B and SNAREs |
title_short |
Identification and Characterization of the Interaction between VPS33B and SNAREs |
title_full |
Identification and Characterization of the Interaction between VPS33B and SNAREs |
title_fullStr |
Identification and Characterization of the Interaction between VPS33B and SNAREs |
title_full_unstemmed |
Identification and Characterization of the Interaction between VPS33B and SNAREs |
title_sort |
identification and characterization of the interaction between vps33b and snares |
publishDate |
2011 |
url |
http://hdl.handle.net/1807/31394 |
work_keys_str_mv |
AT puhaczmichael identificationandcharacterizationoftheinteractionbetweenvps33bandsnares |
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1716583625229598720 |