Rab (G-protein): Difference between revisions
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{{tootechnical|December 2006}} |
{{tootechnical|December 2006}} |
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The '''Rab''' family of [[protein]]s is a member of the [[Ras]] superfamily of monomeric [[G proteins]]. Approximately 70 types of Rabs have now been identified in humans. |
The '''Rab''' family of [[protein]]s is a member of the [[Ras]] superfamily of monomeric [[G proteins]]. Approximately 70 types of Rabs have now been identified in humans. Rab GTPases regulate vesicle formation, vesicle movement along [[actin]] and [[tubulin]] networks, and membrane fusion. |
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==Function== |
==Function== |
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Rab proteins are |
Rab proteins are peripheral membrane proteins, meaning they are anchored to a membrane via a lipid group covalently linked to an amino acid. Specifically, Rabs are anchored via [[prenyl]] groups on two [[cysteines]] in the C-terminus. Rab escort proteins (REPs) deliver newly-synthesized and prenylated Rab to its destination membrane by binding the [[hydrophobic]], insoluble prenyl groups and and carrying Rab through the cytoplasm. The [[lipid]] [[prenyl group]]s can then insert into the membrane, anchoring Rab at the cytoplasmic face of a vesicle or the plasma membrane. Because Rab proteins are anchored to the membrane through a flexible C-terminal region, they can be thought of as a 'balloon on a string'. |
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Like other [[GTPases]], Rabs switch between two conformations, an inactive form bound to GDP (guanosine diphosphate), and an active form bound to GTP (guanosine triphosphate). A GDP/GTP exchange factor (GEF) catalyzes the conversion from GDP-bound to GTP-bound forms, and GTP hydrolysis to GDP is catalyzed by a GTPase-activating protein (GAP). REPs carry only the GDP-bound form of Rab, and Rab effectors, proteins with which Rab interacts and through which it functions, only bind the GTP-bound form of Rab. Rab effectors are very heterogeneous, and each Rab isoform has many effectors through which it carries out multiple functions. |
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Rabs are usually involved in regulating membrane-membrane fusion between vesicles and the plasmatic membrane, a process called regulated exocytosis (regulated secretion). The biological model process for regulated exocytosis is neurotransmitter release from synaptic vesicles into the synaptic cleft. Rabs are anchored at the vesicle membrane and activate vesicle-plasmatic membrane fusion. |
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After membrane fusion, Rab is recycled back to its membrane of origin. A GDP dissociation inhbitor (GDI) binds the prenyl groups of the inactive, GDP-bound form of Rab, inhibits the exchange of GDP for GTP (which would reactivate the Rab) and delivers Rab to its original membrane. |
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Once Rab proteins are bound to a [[vesicle (biology)|vesicle]] surface they can be activated by the replacement of [[guanosine diphosphate]] with GTP ([[catalyst|catalysed]] by [[Guanine]] [[nucleotide]] exchange factors, or GEFs). Rabs bound to GTP are in the active conformation and can now interact with or recruit [[Rab effector]]s on target membranes within the cell. Binding Rab to a Rab effector tethers the vesicle to its appropriate target membrane and allows other membrane surface proteins ([[SNARE]]s) to interact, resulting in the docking of the vesicle to the target membrane. The rest of the process of vesicle exocytosis is Rab independent. |
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Now Rab has fulfilled its function and the GTP is hydrolized to GDP (a step that's enhanced by [[GTPase]] activating proteins, or GAPs). Rab can then be recycled back to their membrane of origin. The GDP dissociation inhbitor (GDI) is necessary for this Rab recycling pathway. GDI binds the prenylated Rab, inhibits the exchange of GDP for GTP (which would reactivate the Rab), solubilizes the prenyl groups (and thus Rab), and delivers Rab to its original membrane. GDI and REP proteins have related functions and are related enzymes. |
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==Clinical significance== |
==Clinical significance== |
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| [[Rab3A]] |
| [[Rab3A]] |
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| secretory |
| secretory vesicles |
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| [[Rab4]] |
| [[Rab4]] |
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| [[Rab5]] |
| [[Rab5]] |
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| early endosomes, plasma membranes |
| early endosomes, clathrin-coated vesicles, plasma membranes |
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| [[Rab6]] |
| [[Rab6]] |
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==References== |
==References== |
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* {{cite journal |author= |
* {{cite journal |author=Stenmark H, Olkkonen VM |title=The Rab GTPase family |journal=Genome Biol |volume=2 |issue=5 |pages=REVIEWS307.1-7 |year=2001 |pmid=11387043}} |
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==External links== |
==External links== |
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Revision as of 22:12, 14 August 2007
 | This December 2006 may be too technical for most readers to understand. |
The Rab family of proteins is a member of the Ras superfamily of monomeric G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab GTPases regulate vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion.
Function
Rab proteins are peripheral membrane proteins, meaning they are anchored to a membrane via a lipid group covalently linked to an amino acid. Specifically, Rabs are anchored via prenyl groups on two cysteines in the C-terminus. Rab escort proteins (REPs) deliver newly-synthesized and prenylated Rab to its destination membrane by binding the hydrophobic, insoluble prenyl groups and and carrying Rab through the cytoplasm. The lipid prenyl groups can then insert into the membrane, anchoring Rab at the cytoplasmic face of a vesicle or the plasma membrane. Because Rab proteins are anchored to the membrane through a flexible C-terminal region, they can be thought of as a 'balloon on a string'.
Like other GTPases, Rabs switch between two conformations, an inactive form bound to GDP (guanosine diphosphate), and an active form bound to GTP (guanosine triphosphate). A GDP/GTP exchange factor (GEF) catalyzes the conversion from GDP-bound to GTP-bound forms, and GTP hydrolysis to GDP is catalyzed by a GTPase-activating protein (GAP). REPs carry only the GDP-bound form of Rab, and Rab effectors, proteins with which Rab interacts and through which it functions, only bind the GTP-bound form of Rab. Rab effectors are very heterogeneous, and each Rab isoform has many effectors through which it carries out multiple functions.
After membrane fusion, Rab is recycled back to its membrane of origin. A GDP dissociation inhbitor (GDI) binds the prenyl groups of the inactive, GDP-bound form of Rab, inhibits the exchange of GDP for GTP (which would reactivate the Rab) and delivers Rab to its original membrane.
Clinical significance
Defects in protein prenylation can cause pathologies such as choroideremia.
Types of Rab proteins
There are approximately 70 different Rabs, mostly involved in vesicle trafficking. Their complexity can be understood if thought of as address labels for vesicle trafficking, defining the identity and routing of vesicles.
| Name | Subcellular location |
|---|---|
| Rab1 (YPT1) | ER, golgi complex |
| Rab2 | ER, cis-golgi network |
| Rab3A | secretory vesicles |
| Rab4 | early endosomes |
| Rab5 | early endosomes, clathrin-coated vesicles, plasma membranes |
| Rab6 | medial- and trans-golgi network |
| Rab7 | late endosomes |
| Rab9 | late endosome, trans-golgi network |
| Rab11 | recycling endosomes |
| Sec4 | secretory vesicles |
Other Rab proteins
References
- Stenmark H, Olkkonen VM (2001). "The Rab GTPase family". Genome Biol. 2 (5): REVIEWS307.1-7. PMID 11387043.
External links
- rab+G-Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)