title: Rab10 GTPase regulates ER dynamics and morphology.
abstract: We have identified Rab10 as an ER-specific Rab GTPase that regulates ER structure and dynamics. We show that Rab10 localizes to the ER and to dynamic ER-associated structures that track along microtubules and mark the position of new ER tubule growth. Rab10 depletion or expression of a Rab10 GDP-locked mutant alters ER morphology, resulting in fewer ER tubules. We demonstrate that this defect is due to a reduced ability of dynamic ER tubules to grow out and successfully fuse with adjacent ER. Consistent with this function, Rab10 partitions to dynamic ER-associated domains found at the leading edge of almost half of all dynamic ER tubules. Interestingly, this Rab10 domain is highly enriched with at least two ER enzymes that regulate phospholipid synthesis, phosphatidylinositol synthase (PIS) and CEPT1. Both the formation and function of this Rab10/PIS/CEPT1 dynamic domain are inhibited by expression of a GDP-locked Rab10 mutant. Together, these data demonstrate that Rab10 regulates ER dynamics and further suggest that these dynamics could be coupled to phospholipid synthesis.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, 80309, USA.
authors.forename: Amber R
authors.initials: AR
authors.lastname: English
authors.forename: Gia K
authors.initials: GK
authors.lastname: Voeltz
mesh_terms: D000818:Animals; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion; D018715:Microscopy, Video; D008870:Microtubules / Q000201:enzymology; D009154:Mutation; D053140:Organelle Shape; D010743:Phospholipids / Q000096:biosynthesis; D021381:Protein Transport; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism; D014982:Xenopus laevis; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D017855:Transferases (Other Substituted Phosphate Groups); C119514:choline-ethanolaminephosphotransferase; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; C538901:Rab10 protein, human; D020691:rab GTP-Binding Proteins