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Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton.

Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. Research Abstract Details 

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  • Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. Abstract Text:

    The spectrin cytoskeleton assembles within discrete regions of the plasma membrane in a wide range of animal cell types. Although recent studies carried out in vertebrate systems indicate that spectrin assembly occurs indirectly through the adapter protein ankyrin, recent studies in Drosophila have established that spectrin can also assemble through a direct ankyrin-independent mechanism. Here we tested specific regions of the spectrin molecule for a role in polarized assembly and function. First, we tested mutant beta-spectrins lacking ankyrin binding activity and/or the COOH-terminal pleckstrin homology (PH) domain for their assembly competence in midgut, salivary gland, and larval brain. Remarkably, three different assembly mechanisms operate in these three cell types: 1) neither site was required for assembly in salivary gland; 2) only the PH domain was required in midgut copper cells; and 3) either one of the two sites was sufficient for spectrin assembly in larval brain. Further characterization of the PH domain revealed that it binds strongly to lipid mixtures containing phosphatidylinositol 4,5-bisphosphate (PIP(2)) but not phosphatidylinositol 3,4,5-trisphosphate. A K8Q mutation in the lipid binding region of the PH domain eliminated the PIP(2) interaction in vitro, yet the mutant protein retained full biological function in vivo. Reporter gene studies revealed that PIP(2) and the spectrin PH domain codistribute with one another in cells but not with authentic wild type alphabeta-spectrin. Thus, it appears that the PH domain imparts membrane targeting activity through a second mechanism that takes precedence over its PIP(2) binding activity.

    Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. Publishing Authors By Initials

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    Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: The Journal of biological chemistry

    VOLUME: 283

    Page Numbers: 12643-53

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 19

    MONTH: 02

    YEAR: 2008

    Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. Information

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    LANGUAGE: eng

    NlmUniqueID: 2985121

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    Grant and Affiliation Information for Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton.

    AFFILIATION: Laboratory for Molecular Biology and Department of Biological Sciences.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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