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Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain.
Wollscheid, Hans-Peter Biancospino, Matteo He, Fahu Magistrati, Elisa Molteni, Erika Lupia, Michela Soffientini, Paolo Rottner, Klemens Cavallaro, Ugo Pozzoli, Uberto
Wollscheid, Hans-Peter
Biancospino, Matteo
He, Fahu
Magistrati, Elisa
Molteni, Erika
Lupia, Michela
Soffientini, Paolo
Rottner, Klemens
Cavallaro, Ugo
Pozzoli, Uberto
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2016-04
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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.
Citation
Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain. 2016, 23 (4):300-308 Nat. Struct. Mol. Biol.
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PubMed Central ID
PMC4964928
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Article
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en
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1545-9985