Rab18 and Rab43 have key roles in ER-Golgi trafficking
| Autor: | Aysegul Erman, Selma Yilmaz Dejgaard, John F. Presley, Jeremy C. Simpson, Rainer Pepperkok, David Verbich, Kurt Dejgaard, Robert Lodge, Thi Bach Nga Ly-Hartig, Ayesha Murshid, Ozge Kizilay |
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| Rok vydání: | 2008 |
| Předmět: |
Recombinant Fusion Proteins
Green Fluorescent Proteins Golgi Apparatus GTPase Biology Endoplasmic Reticulum Models Biological symbols.namesake Microtubule Chlorocebus aethiops Animals Humans Secretion Vero Cells Cells Cultured Secretory pathway Endoplasmic reticulum Cell Biology Golgi apparatus Rats Cell biology Protein Transport rab GTP-Binding Proteins COS Cells symbols Mutant Proteins Rab RAB18 HeLa Cells |
| Zdroj: | Journal of Cell Science. 121:2768-2781 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.021808 |
| Popis: | Rabs and Arfs/Arls are Ras-related small GTPases of particular relevance to membrane trafficking. It is thought that these proteins regulate specific pathways through interactions with coat, motor, tether and SNARE proteins. We screened a comprehensive list of Arf/Arl/Rab proteins, previously identified on purified Golgi membranes by a proteomics approach (37 in total), for Golgi or intra-Golgi localization, dominant-negative and overexpression phenotypes. Further analysis of two of these proteins, Rab18 and Rab43, strongly indicated roles in ER-Golgi trafficking. Rab43-T32N redistributed Golgi elements to ER exit sites without blocking trafficking of the secretory marker VSVG-GFP from ER to cell surface. Wild-type Rab43 redistributes the p150Glued subunit of dynactin, consistent with a specific role in regulating association of pre-Golgi intermediates with microtubules. Overexpression of wild-type GFP-Rab18 or incubation with any of three siRNAs directed against Rab18 severely disrupts the Golgi complex and reduces secretion of VSVG. Rab18 mutants specifically enhance retrograde Golgi-ER transport of the COPI-independent cargo β-1,4-galactosyltransferase (Galtase)-YFP but not the COPI-dependent cargo p58-YFP from the Golgi to ER in a photobleach assay. Rab18-S22N also potentiated brefeldin-A-induced ER-Golgi fusion. This study is the first comprehensive application of large-scale proteomics to the cell biology of small GTPases of the secretory pathway. |
| Databáze: | OpenAIRE |
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