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Article: The adaptor function of TRAPPC2 in mammalian trapps explains TRAPPC2-associated sedt and TRAPPC9-associated congenital intellectual disability

TitleThe adaptor function of TRAPPC2 in mammalian trapps explains TRAPPC2-associated sedt and TRAPPC9-associated congenital intellectual disability
Authors
KeywordsAdaptor protein
Carrier protein
Binding affinity
Cell strain COS1
Complex formation
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 8 How to Cite?
AbstractBackground: The TRAPP (Transport protein particle) complex is a conserved protein complex functioning at various steps in vesicle transport. Although yeast has three functionally and structurally distinct forms, TRAPPI, II and III, emerging evidence suggests that mammalian TRAPP complex may be different. Mutations in the TRAPP complex subunit 2 (TRAPPC2) cause X-linked spondyloepiphyseal dysplasia tarda, while mutations in the TRAPP complex subunit 9 (TRAPPC9) cause postnatal mental retardation with microcephaly. The structural interplay between these subunits found in mammalian equivalent of TRAPPI and those specific to TRAPPII and TRAPPIII remains largely unknown and we undertook the present study to examine the interaction between these subunits. Here, we reveal that the mammalian equivalent of the TRAPPII complex is structurally distinct from the yeast counterpart thus leading to insight into mechanism of disease. Principal Findings: We analyzed how TRAPPII- or TRAPPIII- specific subunits interact with the six-subunit core complex of TRAPP by co-immunoprecipitation in mammalian cells. TRAPPC2 binds to TRAPPII-specific subunit TRAPPC9, which in turn binds to TRAPPC10. Unexpectedly, TRAPPC2 can also bind to the putative TRAPPIII-specific subunit, TRAPPC8. Endogenous TRAPPC9-positive TRAPPII complex does not contain TRAPPC8, suggesting that TRAPPC2 binds to either TRAPPC9 or TRAPPC8 during the formation of the mammalian equivalents of TRAPPII or TRAPPIII, respectively. Therefore, TRAPPC2 serves as an adaptor for the formation of these complexes. A disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9 or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of interaction with TRAPPC9 or TRAPPC8, mediating the formation of TRAPPII and/or TRAPPIII. Furthermore, disease-causing deletional mutants of TRAPPC9 all failed to interact with TRAPPC2 and TRAPPC10. Conclusions: TRAPPC2 serves as an adaptor for the formation of TRAPPII or TRAPPIII in mammalian cells. The mammalian equivalent of TRAPPII is likely different from the yeast TRAPPII structurally. © 2011 Zong et al.
Persistent Identifierhttp://hdl.handle.net/10722/137214
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong UGC GRF479410
Chinese University of Hong Kong
AoE
Funding Information:

This work was supported by Hong Kong UGC GRF grant 479410 (SY), by one-line budget of the Chinese University of Hong Kong (SY) and by AoE grant "Developmental Genomics and Skeletal Research'' (JAT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorZong, Men_HK
dc.contributor.authorWu, Xgen_HK
dc.contributor.authorChan, CWLen_HK
dc.contributor.authorChoi, MYen_HK
dc.contributor.authorChan, HCen_HK
dc.contributor.authorTanner, JAen_HK
dc.contributor.authorYu, Sen_HK
dc.date.accessioned2011-08-26T14:19:01Z-
dc.date.available2011-08-26T14:19:01Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 8en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137214-
dc.description.abstractBackground: The TRAPP (Transport protein particle) complex is a conserved protein complex functioning at various steps in vesicle transport. Although yeast has three functionally and structurally distinct forms, TRAPPI, II and III, emerging evidence suggests that mammalian TRAPP complex may be different. Mutations in the TRAPP complex subunit 2 (TRAPPC2) cause X-linked spondyloepiphyseal dysplasia tarda, while mutations in the TRAPP complex subunit 9 (TRAPPC9) cause postnatal mental retardation with microcephaly. The structural interplay between these subunits found in mammalian equivalent of TRAPPI and those specific to TRAPPII and TRAPPIII remains largely unknown and we undertook the present study to examine the interaction between these subunits. Here, we reveal that the mammalian equivalent of the TRAPPII complex is structurally distinct from the yeast counterpart thus leading to insight into mechanism of disease. Principal Findings: We analyzed how TRAPPII- or TRAPPIII- specific subunits interact with the six-subunit core complex of TRAPP by co-immunoprecipitation in mammalian cells. TRAPPC2 binds to TRAPPII-specific subunit TRAPPC9, which in turn binds to TRAPPC10. Unexpectedly, TRAPPC2 can also bind to the putative TRAPPIII-specific subunit, TRAPPC8. Endogenous TRAPPC9-positive TRAPPII complex does not contain TRAPPC8, suggesting that TRAPPC2 binds to either TRAPPC9 or TRAPPC8 during the formation of the mammalian equivalents of TRAPPII or TRAPPIII, respectively. Therefore, TRAPPC2 serves as an adaptor for the formation of these complexes. A disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9 or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of interaction with TRAPPC9 or TRAPPC8, mediating the formation of TRAPPII and/or TRAPPIII. Furthermore, disease-causing deletional mutants of TRAPPC9 all failed to interact with TRAPPC2 and TRAPPC10. Conclusions: TRAPPC2 serves as an adaptor for the formation of TRAPPII or TRAPPIII in mammalian cells. The mammalian equivalent of TRAPPII is likely different from the yeast TRAPPII structurally. © 2011 Zong et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAdaptor protein-
dc.subjectCarrier protein-
dc.subjectBinding affinity-
dc.subjectCell strain COS1-
dc.subjectComplex formation-
dc.titleThe adaptor function of TRAPPC2 in mammalian trapps explains TRAPPC2-associated sedt and TRAPPC9-associated congenital intellectual disabilityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=6&issue=8, article no. e23350&spage=&epage=&date=2011&atitle=The+adaptor+function+of+TRAPPC2+in+mammalian+TRAPPs+explains+TRAPPC2-associated+SEDT+and+TRAPPC9-associated+congenital+intellectual+disability-
dc.identifier.emailTanner, JA:jatanner@hku.hken_HK
dc.identifier.authorityTanner, JA=rp00495en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pone.0023350en_HK
dc.identifier.pmid21858081-
dc.identifier.pmcidPMC3156116-
dc.identifier.scopuseid_2-s2.0-80051693767en_HK
dc.identifier.hkuros190351en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051693767&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue8en_HK
dc.identifier.isiWOS:000293953700017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZong, M=37119693000en_HK
dc.identifier.scopusauthoridWu, Xg=50061877600en_HK
dc.identifier.scopusauthoridChan, CWL=50060916800en_HK
dc.identifier.scopusauthoridChoi, MY=8309672900en_HK
dc.identifier.scopusauthoridChan, HC=7403402737en_HK
dc.identifier.scopusauthoridTanner, JA=35513993000en_HK
dc.identifier.scopusauthoridYu, S=14055076500en_HK

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