dictyNews
Electronic Edition
Volume 45, number 26
October 11, 2019
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Abstracts
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WASP restricts active Rac to maintain cells’ front-rear polarisation
Clelia Amato, Peter A. Thomason, Andrew J. Davidson, Karthic
Swaminathan, Shehab Ismail, Laura M. Machesky, and Robert H. Insall
Current Biology, in press
Efficient motility requires polarised cells, with pseudopods at the front
and a retracting rear. Polarisation is maintained by restricting the
pseudopod catalyst, active Rac, to the front. Here we show that the actin
nucleation-promoting factor WASP contributes to maintenance of front–
rear polarity, by controlling localisation and cellular levels of active Rac.
Dictyostelium cells lacking WASP inappropriately activate Rac at the rear,
which affects their polarity and speed. WASP’s Rac-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 localises normally at clathrin pits
during endocytosis and activates Arp2/3 complex. Similarly, chemical
inhibition of Rac does not affect WASP localisation 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.
submitted by: Robert Insall [[log in to unmask]]
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