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The membrane strikes back: phosphoinositide binding regulates Skywalker function

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Drosophila Skywalker regulates the GTPase Rab35, thereby controlling the turnover of synaptic-vesicle proteins. A new crystal structure of the TBC domain of Skywalker reveals an unexpected phosphoinositide-binding pocket, which is critical for synaptic function and is disrupted in DOORS syndrome–causing mutations in the human Skywalker homolog TBC1D24.

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Figure 1: The Skywalker (Sky) cationic pocket binds phosphoinositides and is required for normal synaptic trafficking and function.

Marina Corral Spence/Nature Publishing Group

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Authors and Affiliations

  1. Steven J. Del Signore and Avital A. Rodal are at the Department of Biology, Brandeis University, Waltham, Massachusetts, USA.,

    Steven J Del Signore & Avital A Rodal

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  1. Steven J Del Signore
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  2. Avital A Rodal
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Correspondence to Avital A Rodal.

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The authors declare no competing financial interests.

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Del Signore, S., Rodal, A. The membrane strikes back: phosphoinositide binding regulates Skywalker function. Nat Struct Mol Biol 23, 956–957 (2016). https://doi.org/10.1038/nsmb.3313

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