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    WASP restricts active Rac to maintain cells' front-rear polarization

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    Swaminathan_Current_Biology_2019.pdf (5.334Mb)
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    Publication date
    2019-12
    Author
    Amato, C.
    Thomason, P.A.
    Davidson, A.J.
    Swaminathan, Karthic
    Ismail, S.
    Machesky, L.M.
    Insall, R.H.
    Keyword
    Actin polymerization
    Arp2/3 complex
    Cell polarity
    Uropod
    Small GTPases
    CRIB motif
    Actin cytoskeleton
    Rights
    © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Efficient motility requires polarized cells, with pseudopods at the front and a retracting rear. Polarization is maintained by restricting the pseudopod catalyst, active Rac, to the front. Here, we show that the actin nucleation-promoting factor Wiskott-Aldrich syndrome protein (WASP) contributes to maintenance of front-rear polarity by controlling localization and cellular levels of active Rac. Dictyostelium cells lacking WASP inappropriately activate Rac at the rear, which affects their polarity and speed. WASP’s Cdc42 and Rac interacting binding (“CRIB”) motif has been thought to be essential for its activation. However, we show that the CRIB motif’s biological role is unexpectedly complex. WASP CRIB mutants are no longer able to restrict Rac activity to the front, and cannot generate new pseudopods when SCAR/WAVE is absent. Overall levels of Rac activity also increase when WASP is unable to bind to Rac. However, WASP without a functional CRIB domain localizes normally at clathrin pits during endocytosis, and activates Arp2/3 complex. Similarly, chemical inhibition of Rac does not affect WASP localization or activation at sites of endocytosis. Thus, the interaction between small GTPases and WASP is more complex than previously thought—Rac regulates a subset of WASP functions, but WASP reciprocally restricts active Rac through its CRIB motif.
    URI
    http://hdl.handle.net/10454/17714
    Version
    Published version
    Citation
    Amato C, Thomason PA, Davidson AJ et al (2019) WASP restricts active Rac to maintain cells' front-rear polarization. Current Biology. 29(24): 4169-4182.e4.
    Link to publisher’s version
    https://doi.org/10.1016/j.cub.2019.10.036
    Type
    Article
    Collections
    Life Sciences Publications

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