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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Main Author: Puhacz, Michael
Other Authors: Kahr, Walter
Language:en_ca
Published: 2011
Subjects:
Online Access:http://hdl.handle.net/1807/31394
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spelling 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
collection NDLTD
language en_ca
sources NDLTD
topic SNAREs
Sec1/Munc18
VPS33B
syntaxin-6
megakaryocyte
platelet
0379
spellingShingle 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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