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SWAP70 undergoes dynamic conformational regulation at the leading edge of migrating cells
Author(s) -
Kriplani Nisha,
Duncan Rory R.,
Leslie Nicholas R.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13326
Subject(s) - rac1 , gtpase , förster resonance energy transfer , microbiology and biotechnology , actin , biophysics , cytoskeleton , conformational change , actin cytoskeleton , chemistry , biology , biochemistry , signal transduction , cell , fluorescence , physics , quantum mechanics
Rearrangements of the actin cytoskeleton are regulated in part by dynamic localised activation and inactivation of Rho family small GTP ases. SWAP 70 binds to and activates the small GTP ase RAC 1 as well as binding to filamentous actin and PIP 3 . We have developed an encoded biosensor, which uses Forster resonance energy transfer to reveal conformational changes in SWAP 70 in live cells. SWAP 70 adopts a distinct conformation at the plasma membrane, which in migrating glioma cells is enriched at the leading edge but does not always associate with its PIP 3 ‐dependent translocation to the membrane. This supports a role for SWAP 70 in positive feedback activation of RAC 1 at sites of filamentous actin, PIP 3 and active RAC 1.