2.50
Hdl Handle:
http://hdl.handle.net/10033/621298
Title:
Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain.
Authors:
Wollscheid, Hans-Peter; Biancospino, Matteo; He, Fahu; Magistrati, Elisa; Molteni, Erika; Lupia, Michela; Soffientini, Paolo; Rottner, Klemens; Cavallaro, Ugo; Pozzoli, Uberto; Mapelli, Marina; Walters, Kylie J; Polo, Simona
Abstract:
Myosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VI(short) and myosin VI(long), which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the α2-linker structurally defines a new clathrin-binding domain that is unique to myosin VI(long) and masks the known RRL interaction motif. This finding is relevant to ovarian cancer, in which alternative myosin VI splicing is aberrantly regulated, and exon skipping dictates cell addiction to myosin VI(short) in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VI(short). Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain. 2016, 23 (4):300-308 Nat. Struct. Mol. Biol.
Journal:
Nature structural & molecular biology
Issue Date:
Apr-2016
URI:
http://hdl.handle.net/10033/621298
DOI:
10.1038/nsmb.3187
PubMed ID:
26950368
PubMed Central ID:
PMC4964928
Additional Links:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964928/
Type:
Article
Language:
en
ISSN:
1545-9985
Appears in Collections:
publications of the Research group: molecular cell biology (MZBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorWollscheid, Hans-Peteren
dc.contributor.authorBiancospino, Matteoen
dc.contributor.authorHe, Fahuen
dc.contributor.authorMagistrati, Elisaen
dc.contributor.authorMolteni, Erikaen
dc.contributor.authorLupia, Michelaen
dc.contributor.authorSoffientini, Paoloen
dc.contributor.authorRottner, Klemensen
dc.contributor.authorCavallaro, Ugoen
dc.contributor.authorPozzoli, Ubertoen
dc.contributor.authorMapelli, Marinaen
dc.contributor.authorWalters, Kylie Jen
dc.contributor.authorPolo, Simonaen
dc.date.accessioned2018-02-27T13:03:42Z-
dc.date.available2018-02-27T13:03:42Z-
dc.date.issued2016-04-
dc.identifier.citationDiverse functions of myosin VI elucidated by an isoform-specific α-helix domain. 2016, 23 (4):300-308 Nat. Struct. Mol. Biol.en
dc.identifier.issn1545-9985-
dc.identifier.pmid26950368-
dc.identifier.doi10.1038/nsmb.3187-
dc.identifier.urihttp://hdl.handle.net/10033/621298-
dc.description.abstractMyosin VI functions in endocytosis and cell motility. Alternative splicing of myosin VI mRNA generates two distinct isoform types, myosin VI(short) and myosin VI(long), which differ in the C-terminal region. Their physiological and pathological roles remain unknown. Here we identified an isoform-specific regulatory helix, named the α2-linker, that defines specific conformations and hence determines the target selectivity of human myosin VI. The presence of the α2-linker structurally defines a new clathrin-binding domain that is unique to myosin VI(long) and masks the known RRL interaction motif. This finding is relevant to ovarian cancer, in which alternative myosin VI splicing is aberrantly regulated, and exon skipping dictates cell addiction to myosin VI(short) in tumor-cell migration. The RRL interactor optineurin contributes to this process by selectively binding myosin VI(short). Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles.en
dc.language.isoenen
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964928/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCell Movementen
dc.subject.meshClathrinen
dc.subject.meshFemaleen
dc.subject.meshGene Knockout Techniquesen
dc.subject.meshHumansen
dc.subject.meshModels, Molecularen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMyosin Heavy Chainsen
dc.subject.meshNeoplasmsen
dc.subject.meshNuclear Magnetic Resonance, Biomolecularen
dc.subject.meshOvarian Neoplasmsen
dc.subject.meshProtein Interaction Mapsen
dc.subject.meshProtein Isoformsen
dc.subject.meshProtein Structure, Secondaryen
dc.subject.meshProtein Structure, Tertiaryen
dc.titleDiverse functions of myosin VI elucidated by an isoform-specific α-helix domain.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalNature structural & molecular biologyen
dc.identifier.pmcidPMC4964928-

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