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| Content Provider | Springer Nature Link |
|---|---|
| Author | Wright, John Kahn, Richard A. Sztul, Elizabeth |
| Copyright Year | 2014 |
| Abstract | Eukaryotic cells require selective sorting and transport of cargo between intracellular compartments. This is accomplished at least in part by vesicles that bud from a donor compartment, sequestering a subset of resident protein “cargos” destined for transport to an acceptor compartment. A key step in vesicle formation and targeting is the recruitment of specific proteins that form a coat on the outside of the vesicle in a process requiring the activation of regulatory GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive, GDP-bound, and membrane-associated active, GTP-bound, conformations. And like most regulatory GTPases the activating step is slow and thought to be rate limiting in cells, requiring the use of ARF guanine nucleotide exchange factor (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7 domain, though they also contain motifs or additional domains that confer specificity to localization and regulation of activity. These domains have been used to define and classify five different sub-families of ARF GEFs. One of these, the BIG/GBF1 family, includes three proteins that are each key regulators of the secretory pathway. GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs and thus these GEFs are the upstream regulators that define the site and timing of vesicle production. Paradoxically, while we have detailed molecular knowledge of how GEFs activate ARFs, we know very little about how GEFs are recruited and/or activated at the right time and place to initiate transport. This review summarizes the current knowledge of GEF regulation and explores the still uncertain mechanisms that position GEFs at “budding ready” membrane sites to generate highly localized activated ARFs. |
| Starting Page | 3419 |
| Ending Page | 3438 |
| Page Count | 20 |
| File Format | |
| ISSN | 1420682X |
| Journal | Cellular and Molecular Life Sciences |
| Volume Number | 71 |
| Issue Number | 18 |
| e-ISSN | 14209071 |
| Language | English |
| Publisher | Springer Basel |
| Publisher Date | 2014-04-13 |
| Publisher Place | Basel |
| Access Restriction | Subscribed |
| Subject Keyword | Membrane traffic ARF GTPases Guanine nucleotide exchange factors (GEFs) COP-I and clathrin coats Adaptor proteins Cell Biology Biomedicine general Life Sciences Biochemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience |
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