Dissecting the role of the ARF guanine nucleotide exchange factor GBF1 in Golgi biogenesis and protein trafficking
| Autor: | Robert Grabski, Tomasz Szul, Svetlana A. Shestopal, Martin Lowe, Elizabeth Sztul, Susan A. Lyons, Yuichi Morohashi |
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| Rok vydání: | 2007 |
| Předmět: |
Golgi Apparatus
Biology Endoplasmic Reticulum Models Biological Coat Protein Complex I symbols.namesake chemistry.chemical_compound Cell Movement Guanine Nucleotide Exchange Factors Humans Secretory pathway ADP-Ribosylation Factors Vesicular-tubular cluster Endoplasmic reticulum Membrane Proteins Cell Biology COPI Golgi apparatus Brefeldin A Transmembrane protein Cell Compartmentation Cell biology Protein Transport Solubility chemistry symbols ADP-Ribosylation Factor 1 Guanine nucleotide exchange factor HeLa Cells Protein Binding |
| Zdroj: | Journal of Cell Science. 120:3929-3940 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.010769 |
| Popis: | COPI recruitment to membranes appears to be essential for the biogenesis of the Golgi and for secretory trafficking. Preventing COPI recruitment by expressing inactive forms of the ADP-ribosylation factor (ARF) or the ARF-activating guanine nucleotide exchange factor GBF1, or by treating cells with brefeldin A (BFA), causes the collapse of the Golgi into the endoplasmic reticulum (ER) and arrests trafficking of soluble and transmembrane proteins at the ER. Here, we assess COPI function in Golgi biogenesis and protein trafficking by preventing COPI recruitment to membranes by removing GBF1. We report that siRNA-mediated depletion of GBF1 causes COPI dispersal but does not lead to collapse of the Golgi. Instead, it causes extensive tubulation of the cis-Golgi. The Golgi-derived tubules target to peripheral ER-Golgi intermediate compartment (ERGIC) sites and create dynamic continuities between the ERGIC and the cis-Golgi compartment. COPI dispersal in GBF1-depleted cells causes dramatic inhibition of the trafficking of transmembrane proteins. Unexpectedly, soluble proteins continue to be secreted from GBF1-depleted cells. Our findings suggest that a secretory pathway capable of trafficking soluble proteins can be maintained in cells in which COPI recruitment is compromised by GBF1 depletion. However, the trafficking of transmembrane proteins through the existing pathway requires GBF1-mediated ARF activation and COPI recruitment. |
| Databáze: | OpenAIRE |
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