5 years ago

Human Rab GTPase- and class V myosin-mediated membrane tethering in a chemically defined reconstitution system [Revised]

J., M., Inoshita, Mima
Membrane tethering is a fundamental reaction to confer the compartmental specificity of intracellular membrane trafficking in eukaryotic cells. Rab-family small GTPases and specific sets of Rab-interacting effector proteins, including coiled-coil tethering proteins and multisubunit tethering complexes, have been reported to be responsible for membrane tethering. However, whether and how indeed these key components directly and specifically tether subcellular membranes still remain enigmatic. Using the chemically defined systems reconstituted with purified human Rab proteins and synthetic liposomal membranes, we now establish that Rab-family GTPases have the highly conserved function to directly mediate membrane tethering, even in the absence of any types of Rab effectors such as the so-called tethering proteins. Moreover, we strikingly demonstrate that membrane tethering mediated by endosomal Rab11a is drastically and selectively stimulated by its cognate Rab effectors, class V myosins (Myo5A and Myo5B), in a GTP-dependent manner. Myo5A and Myo5B exclusively recognize and cooperate with the membrane-anchored form of the cognate Rab11a to support membrane tethering mediated by trans-Rab assemblies on apposing membranes. These current findings postulate the novel concept that Rab-family proteins are a bona fide membrane tether to physically and specifically link two distinct lipid bilayers of subcellular membranes, and Rab-interacting effector proteins, including class V myosins, can be rather a regulator of Rab-mediated membrane tethering reactions.

Publisher URL: http://biorxiv.org/cgi/content/short/129072v3

DOI: 10.1101/129072

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