Molecular principles of bidirectional signalling between membranes and small GTPases.

Agata Nawrotek, Pavlina Dubois, Mahel Zeghouf, Jacqueline Cherfils

FEBS letters 2023 Mar

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Most small GTPases actuate their functions on subcellular membranes, which are increasingly seen as integral components of small GTPase signalling. In this review, we used the highly studied regulation of Arf GTPases by their GEFs to categorize the molecular principles of membrane contributions to small GTPase signalling, which have been highlighted by integrated structural biology combining in vitro reconstitutions in artificial membranes and high-resolution structures. As an illustration of how this framework can be harnessed to better understand the cooperation between small GTPases, their regulators and membranes, we applied it to the activation of the small GTPase Rac1 by DOCK-ELMO, identifying novel contributions of membranes to Rac1 activation. We propose that these structure-based principles should be considered when interrogating the mechanisms whereby small GTPase systems ensure spatial and temporal control of cellular signalling on membranes. © 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Citation

Agata Nawrotek, Pavlina Dubois, Mahel Zeghouf, Jacqueline Cherfils. Molecular principles of bidirectional signalling between membranes and small GTPases. FEBS letters. 2023 Mar;597(6):778-793