Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels

Dervla O'Malley, Andrew J. Irving, Jenni Harvey

    Research output: Contribution to journalArticle

    53 Citations (Scopus)

    Abstract

    Phosphoinositide 3-kinase (PI3-kinase) has been shown to link leptin receptor activation to stimulation of large conductance Ca2+-activated K+ (BK) channels and subsequent inhibition of hippocampal epileptiform-like activity. However, the downstream targets of PI3-kinase in this action of leptin are unknown. Here we show that BK channel activation by leptin is dependent on the actin cytoskeleton, as it is prevented by actin filament stabilization and mimicked by actin disruption. Fluorescent labeling of polymerized actin filaments revealed that leptin promotes the rapid rearrangement of actin filaments via activation of PI 3-kinase; an action paralleled by discrete increases in PtdIns(3,4,5)P3 immunoreactivity in close proximity to BK channels. After leptin exposure, there was also an actin-dependent increase in the association of BK channel immunoreactivity with synaptic markers. These data are consistent with the notion that leptin activates BK channels via PI 3-kinase-dependent reorganization of actin filaments and subsequent clustering of BK channels at synapses.
    Original languageEnglish
    Pages (from-to)1917-1919
    Number of pages3
    JournalFASEB Journal
    Volume19
    Issue number11
    DOIs
    Publication statusPublished - Nov 2005

    Fingerprint

    Large-Conductance Calcium-Activated Potassium Channels
    Leptin
    Actin Cytoskeleton
    Cluster Analysis
    Actins
    Chemical activation
    1-Phosphatidylinositol 4-Kinase
    Phosphatidylinositol 3-Kinases
    Phosphatidylinositols
    Phosphotransferases
    Calcium-Activated Potassium Channels
    Leptin Receptors
    Synapses
    Labeling
    Stabilization
    Association reactions

    Keywords

    • PI 3-kinase
    • Actin cytoskeleton
    • PtdIns(3,4,5)P3

    Cite this

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    abstract = "Phosphoinositide 3-kinase (PI3-kinase) has been shown to link leptin receptor activation to stimulation of large conductance Ca2+-activated K+ (BK) channels and subsequent inhibition of hippocampal epileptiform-like activity. However, the downstream targets of PI3-kinase in this action of leptin are unknown. Here we show that BK channel activation by leptin is dependent on the actin cytoskeleton, as it is prevented by actin filament stabilization and mimicked by actin disruption. Fluorescent labeling of polymerized actin filaments revealed that leptin promotes the rapid rearrangement of actin filaments via activation of PI 3-kinase; an action paralleled by discrete increases in PtdIns(3,4,5)P3 immunoreactivity in close proximity to BK channels. After leptin exposure, there was also an actin-dependent increase in the association of BK channel immunoreactivity with synaptic markers. These data are consistent with the notion that leptin activates BK channels via PI 3-kinase-dependent reorganization of actin filaments and subsequent clustering of BK channels at synapses.",
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    Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels. / O'Malley, Dervla; Irving, Andrew J.; Harvey, Jenni.

    In: FASEB Journal, Vol. 19, No. 11, 11.2005, p. 1917-1919.

    Research output: Contribution to journalArticle

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