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bioRxiv · 10.1101/2019.12.17.880203

A non-linear system patterns Rab5 GTPase on the membrane

Cezanne, A.·Lauer, J.·Solomatina, A.·Sbalzarini, I. F.·Zerial, M.
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Abstract

Proteins can self-organize into spatial patterns via non-linear dynamic interactions on cellular membranes. Modelling and simulations have shown that small GTPases can generate patterns by coupling guanine nucleotide exchange factors (GEF) to effector binding, generating a positive feedback of GTPase activation and membrane recruitment. Here, we reconstituted the patterning of the small GTPase Rab5 and its GEF/effector complex Rabex5/Rabaptin5 on supported lipid bilayers as a model system for membrane patterning. We show that there is a "handover" of Rab5 from Rabex5 to Rabaptin5 upon nucleotide exchange. A minimal system consisting of Rab5, RabGDI and a complex of full length Rabex5/Rabaptin5 was necessary to pattern Rab5 into membrane domains. Surprisingly, a lipid membrane composition mimicking that of the early endosome was required for Rab5 patterning. The prevalence of GEF/effector coupling in nature suggests a possible universal system for small GTPase patterning involving both protein and lipid interactions.

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Cezanne, A., Lauer, J., Solomatina, A., Sbalzarini, I. F., Zerial, M.. 2019-12-18. A non-linear system patterns Rab5 GTPase on the membrane. https://doi.org/10.1101/2019.12.17.880203

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