Membrane extraction by calmodulin underpins the disparate signalling of RalA and RalB.

Publisher: Wiley Country of Publication: United States NLM ID: 8510851 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-1878 (Electronic) Linking ISSN: 02659247 NLM ISO Abbreviation: Bioessays Subsets: MEDLINE

Publication: <2005->: Hoboken, N.J. : Wiley
Original Publication: Cambridge, UK : Published for the ICSU Press by Cambridge University Press, c1984-

Calmodulin*/metabolism ; Signal Transduction*; GTP Phosphohydrolases/metabolism ; Protein Isoforms/metabolism

Both RalA and RalB interact with the ubiquitous calcium sensor, calmodulin (CaM). New structural and biophysical characterisation of these interactions strongly suggests that, in the native membrane-associated state, only RalA can be extracted from the membrane by CaM and this non-canonical interaction could underpin the divergent signalling roles of these closely related GTPases. The isoform specificity for RalA exhibited by CaM is hypothesised to contribute to the disparate signalling roles of RalA and RalB in mitochondrial dynamics. This would lead to CaM shuttling RalA to the mitochondrial membrane but leaving RalB localisation unperturbed, and in doing so triggering mitochondrial fission pathways rather than mitophagy.
(© 2022 The Authors. BioEssays published by Wiley Periodicals LLC.)

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BB/E013228/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/P504853/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council

Keywords: RalA; RalB; calmodulin; isoprenylation; membrane binding; mitochondria; small GTPase

0 (Calmodulin)
0 (Protein Isoforms)
EC 3.6.1.- (GTP Phosphohydrolases)

Date Created: 20220323 Date Completed: 20220524 Latest Revision: 20230705

20240829

10.1002/bies.202200011

35318680