A role for Rab5 in structuring the endoplasmic reticulum.
The endoplasmic reticulum (ER) is a contiguous network of interconnected membrane sheets and tubules. The ER is differentiated into distinct domains, including the peripheral ER and nuclear envelope. Inhibition of two ER proteins, Rtn4a and DP1/NogoA, was previously shown to inhibit the formation of ER tubules in vitro. We show that the formation of ER tubules in vitro also requires a Rab family GTPase. Characterization of the 29 Caenorhabditis elegans Rab GTPases reveals that depletion of RAB-5 phenocopies the defects in peripheral ER structure that result from depletion of RET-1 and YOP-1, the C. elegans homologues of Rtn4a and DP1/NogoA. Perturbation of endocytosis by other means did not affect ER structure; the role of RAB-5 in ER morphology is thus independent of its well-studied requirement for endocytosis. RAB-5 and YOP-1/RET-1 also control the kinetics of nuclear envelope disassembly, which suggests an important role for the morphology of the peripheral ER in this process.
Audhya
Anjon
A
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA. aaudhya@ucsd.edu
Desai
Arshad
A
Oegema
Karen
K
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D002457:Cell Extracts / Q000737:chemistry; D004625:Embryo, Nonmammalian; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010063:Ovum / Q000737:chemistry; D034622:RNA Interference; D018510:RNA, Helminth; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014982:Xenopus laevis; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
D002457:Cell Extracts; D006657:Histones; D018510:RNA, Helminth; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020696:rab5 GTP-Binding Proteins