Reconstitution of membrane tethering mediated by Rab-family small GTPases
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Membrane tethering is one of the most critical steps to determine the spatiotemporal specificity of membrane trafficking, which is the process to selectively transport proteins, lipids, and other biological molecules to the appropriate locations in eukaryotic cells, such as subcellular organelles, the plasma membrane, and the extracellular space. Based on genetic, cell biological, biochemical, and structural studies, Rab-family small GTPases and a number of Rab-interacting proteins (termed Rab effectors), including coiled-coil tethering proteins and multisubunit tethering complexes, have been proposed to be key protein components for membrane tethering. Nevertheless, indeed whether and how Rab GTPases and their specific Rab effectors directly act upon and catalyze membrane tethering still remains enigmatic. By chemically defined reconstitution of membrane tethering from purified Rab-family GTPase proteins and synthetic liposomal membranes, recent studies have revealed the intrinsic potency of Rab-family GTPases to physically and specifically tether two distinct lipid bilayers of liposomal membranes. Experimental evidence from these reconstitution studies support the novel working model in which Rab-family small GTPases act as a bona fide membrane tether for mediating membrane tethering events in eukaryotic membrane trafficking.
KeywordsMembrane reconstitution Membrane trafficking Membrane tethering Rab protein Small GTPase Liposome
The author is grateful to Dr. Naoki Tamura (Institute for Protein Research, Osaka University, now Fukushima Medical University School of Medicine) for his substantial contributions to embarking on the research projects of human Rab-mediated membrane tethering. This work was, in part, supported by the Program to Disseminate Tenure Tracking System from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and Grants-in-Aid for Scientific Research from MEXT (to J.M.).
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Conflict of interest
Joji Mima declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by the author.
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