RAB11B

Last updated
RAB11B
Protein RAB11B PDB 1oiv.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RAB11B , H-YPT3, member RAS oncogene family, NDAGSCW
External IDs OMIM: 604198 MGI: 99425 HomoloGene: 68691 GeneCards: RAB11B
Orthologs
SpeciesHumanMouse
Entrez

9230

19326

Ensembl

ENSG00000185236

ENSMUSG00000077450

UniProt

Q15907

P46638

RefSeq (mRNA)

NM_004218

NM_008997

RefSeq (protein)

NP_004209

NP_033023

Location (UCSC) Chr 19: 8.39 – 8.4 Mb Chr 17: 33.96 – 33.98 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ras-related protein Rab-11B is a protein that in humans is encoded by the RAB11B gene. [5] [6] Rab11b is reported as most abundantly expressed in brain, heart and testes.

Contents

Rab (Ras-related in brain) proteins form the largest section of the Ras superfamily of small GTPases. The Rab family proteins regulate intracellular membrane trafficking processes including vesicle budding, tethering, and fusion. The isoforms Rab11a, Rab11b, and Rab11c/Rab25 constitute the Rab11 subfamily based on specific sequence motifs. [7] While RAB11A is located on chromosome 15 [8] and RAB11C on chromosome 1, RAB11B is placed on chromosome 19. Rab11 proteins are implicated in endocytosis and exocytosis. [9] Rab11b is reported as most abundantly expressed in brain, heart and testes. [10] Early studies with deletions of RAB11 homologs in Saccharomyces cerevisiae proved their importance in cell survival. [11] [12] Despite sharing high sequence homology, Rab11a and Rab11b appear to reside within distinct vesicle compartments. [13] Majority of Rab11b neither colocalize with transferrin receptor nor with the polymeric IgA receptor. This protein also exhibits a dependence on the microtubule cytoskeleton that is different from Rab11a. [13] High sequence diversity in the C-terminal hypervariable region is responsible for variable membrane targeting between these proteins.

Function

Members of the Rab11 subfamily act in recycling of proteins from the endosomes to the plasma membrane, in transport of molecules from the trans-Golgi network to the plasma membrane and in phagocytosis. This subfamily also acts in polarized transport in epithelial cells. [14] [15] [16] [17] [18] Whereas most studies refer to the Rab11a isoform, little is known about Rab11b so far. Rab11b localizes predominantly in the pericentriolar recycling compartment and serves as an important component of the vesicular machinery. [19] It is required for the transfer of internalized transferrin from the recycling compartment to the plasma membrane for which active Rab11b as well as GTP hydrolysis is necessary. [19]

Structure

All Ras GTPases consist of a similar core structure and highly conserved P-loop, switch 1 and switch 2 regions. The Rab11b monomer exhibits a typical Ras-like, small GTPase fold with a six stranded β-sheet core (β1-β6) surrounded by five major α-helices (α1-α5) [16] and one minor α-helix (α6). According to the sequence similarity to other Rab GTPases can be assumed that they show closely resembling characteristics in nucleotide binding and hydrolysis. However, Rab11 isoforms could differ in hydrolysis kinetics owing to the differences in conformation, since Rab11a and Rab11b do not show an α-helical switch 2 region like other Rab GTPases. Rab11b shares 90% amino acid identity to Rab11a. [16] Kinetic experiments with Rab11a/b and Rab11-interacting proteins (FIPs) indicate that FIPs cannot differentiate between GTP-bound Rab11a and Rab11b in vitro. [20] The major divergence reveals in the inactive state. While Pasqualato et al. crystallized inactive Rab11a as a dimer in the asymmetric unit, Scapin et al. observed single crystallographically independent monomers of both the GDP- and the GppNHp-bound Rab11b structures. [16] [21]

Cartoon model of active Rab11b-GppNP complex (PDB-ID: 2F9M ). This model includes amino acids 8-188. The model shows classic Ras-like structure with a six stranded beta sheet core encircled by 5 major and one minor a-helix. GppNp and Mg2+ form polar bonds with the residues S20, K24, S25, N27, S40/S42/T43 (switch1), N124, K125, D127, S154, and with some parts of the backbone highlighted in olive green. Hydrogen-bonds are drawn as black dots. Atoms of GppNP, Mg2+, and sidechains are colored corresponding to their element. O = red, N = blue, P = orange, and Mg = green. The purple sequence represents the Rab-typical a310 helix region. Rab11b-GNP-bind.png
Cartoon model of active Rab11b-GppNP complex (PDB-ID: 2F9M ). This model includes amino acids 8–188. The model shows classic Ras-like structure with a six stranded beta sheet core encircled by 5 major and one minor α-helix. GppNp and Mg2+ form polar bonds with the residues S20, K24, S25, N27, S40/S42/T43 (switch1), N124, K125, D127, S154, and with some parts of the backbone highlighted in olive green. Hydrogen-bonds are drawn as black dots. Atoms of GppNP, Mg2+, and sidechains are colored corresponding to their element. O = red, N = blue, P = orange, and Mg = green. The purple sequence represents the Rab-typical α310 helix region.
Alignment of inactive and active Rab11b (PDB-IDs: 2F9L/2F9M ). The alignment shows slight conformational differences between the GDP- and the GppNP-bound form. Major divergences are displayed in red. The Rab11b-GDP structure shows the a310 helix in the switch 2 region whereas Rab11b-GppNP does not. Rab11b-GDP model lacks in the switch 1 section 39-41. These amino acids could not be modeled from the electron density map. Due to the lack in switch 1 structure, the two states are not comparable from these models. Furthermore, the inactive state shows a truncated a-6 helix. Alignment mod.png
Alignment of inactive and active Rab11b (PDB-IDs: 2F9L/2F9M ). The alignment shows slight conformational differences between the GDP- and the GppNP-bound form. Major divergences are displayed in red. The Rab11b-GDP structure shows the α310 helix in the switch 2 region whereas Rab11b-GppNP does not. Rab11b-GDP model lacks in the switch 1 section 39–41. These amino acids could not be modeled from the electron density map. Due to the lack in switch 1 structure, the two states are not comparable from these models. Furthermore, the inactive state shows a truncated α-6 helix.

Clinical significance

Due to their crucial importance in vesicle transport and recycling, Rab11 proteins are linked to various non-pathogen or pathogen induced diseases. Most of the published data do not specify whether it is the a- or the b-isoform. Rab11 proteins have been implicated in Alzheimer's disease, [22] [23] Arthrogryposis-renal dysfunction-cholestasis (ARC), [24] Batten disease, [25] and Charcot-Marie-Tooth Neuropathy Type 4C (CMT4C). [26] Intracellular bacteria Chlamydia pneumoniae and Chlamydia trachomatis that replicate in membrane bound compartments hijack the trafficking machinery recruiting Rab GTPases to promote their replication within the host cell. Knock down of Rab11 decreased the formation of infectious particles. [27] [28] [29] Recent studies report a similar use of intracellular trafficking by Hantavirus and Influenza A virus. Replicated viruses benefit from Rab11 mediated recycling endosome pathway to exit the cell and infect surrounding tissue. [30] [31] [32] [33]

Related Research Articles

<span class="mw-page-title-main">Endocytosis</span> Cellular process

Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis and phagocytosis. It is a form of active transport.

<span class="mw-page-title-main">Golgi apparatus</span> Cell organelle that packages proteins for export

The Golgi apparatus, also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. It is of particular importance in processing proteins for secretion, containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus.

The Coat Protein Complex II, or COPII, is a group of proteins that facilitate the formation of vesicles to transport proteins from the endoplasmic reticulum to the Golgi apparatus or endoplasmic-reticulum–Golgi intermediate compartment. This process is termed anterograde transport, in contrast to the retrograde transport associated with the COPI complex. COPII is assembled in two parts: first an inner layer of Sar1, Sec23, and Sec24 forms; then the inner coat is surrounded by an outer lattice of Sec13 and Sec31.

<span class="mw-page-title-main">Endosome</span> Vacuole to which materials ingested by endocytosis are delivered

Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus.

The Rab family of proteins is a member of the Ras superfamily of small G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab proteins generally possess a GTPase fold, which consists of a six-stranded beta sheet which is flanked by five alpha helices. Rab GTPases regulate many steps of membrane trafficking, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface.

Retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the trans-Golgi network (TGN) and directly back to the plasma membrane. Mutations in retromer and its associated proteins have been linked to Alzheimer's and Parkinson's diseases.

<span class="mw-page-title-main">RAB5A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.

<span class="mw-page-title-main">RAB7A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.

<span class="mw-page-title-main">RAB11A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-11A is a protein that in humans is encoded by the RAB11A gene.

<span class="mw-page-title-main">RAB8A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-8A is a protein that in humans is encoded by the RAB8A gene.

<span class="mw-page-title-main">VAMP3</span> Protein-coding gene in the species Homo sapiens

Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.

<span class="mw-page-title-main">RAB11FIP1</span> Protein-coding gene in the species Homo sapiens

Rab11 family-interacting protein 1 (Rab11-FIP1) also known as Rab-coupling protein is a protein that in humans is encoded by the RAB11FIP1 gene.

<span class="mw-page-title-main">RAB11FIP2</span> Protein-coding gene in the species Homo sapiens

Rab11 family-interacting protein 2 is a protein that in humans is encoded by the RAB11FIP2 gene.

<span class="mw-page-title-main">RAB11FIP5</span> Protein-coding gene in the species Homo sapiens

Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.

<span class="mw-page-title-main">RAB11FIP3</span> Protein-coding gene in the species Homo sapiens

Rab11 family-interacting protein 3 is a protein that in humans is encoded by the RAB11FIP3 gene.

<span class="mw-page-title-main">RAB22A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-22A is a protein that in humans is encoded by the RAB22A gene.

<span class="mw-page-title-main">RAB25</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-25 is a protein that in humans is encoded by the RAB25 gene. It is thought to act as a promoter of tumor development.

The EHD protein family is a relatively small group of proteins which have been shown to play a role in several physiological functions, the most notable being the regulation of endocytotic vesicles. This family is recognized by its highly conserved EH domain, a structural motif that has been shown to facilitate specificity and interaction between protein and ligand. The four mammalian EHD proteins that have been classified are: EHD1, EHD2, EHD3, and EHD4.

Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory cell. It takes place in the form of Golgi membrane-bound micro-sized vesicles, termed membrane vesicles (MVs).

<span class="mw-page-title-main">RAB2B</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-2B is a protein that in humans is encoded by the RAB2B gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185236 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000077450 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Zhu AX, Zhao Y, Flier JS (Dec 1994). "Molecular cloning of two small GTP-binding proteins from human skeletal muscle". Biochemical and Biophysical Research Communications. 205 (3): 1875–82. doi:10.1006/bbrc.1994.2889. PMID   7811277.
  6. ↑ "Entrez Gene: RAB11B RAB11B, member RAS oncogene family".
  7. ↑ Bhartur SG, Calhoun BC, Woodrum J, Kurkjian J, Iyer S, Lai F, Goldenring JR (Mar 2000). "Genomic structure of murine Rab11 family members". Biochemical and Biophysical Research Communications. 269 (2): 611–7. doi:10.1006/bbrc.2000.2334. PMID   10708602.
  8. ↑ Gromov PS, Celis JE, Hansen C, Tommerup N, Gromova I, Madsen P (Jun 1998). "Human rab11a: transcription, chromosome mapping and effect on the expression levels of host GTP-binding proteins". FEBS Letters. 429 (3): 359–64. doi: 10.1016/s0014-5793(98)00607-3 . PMID   9662449. S2CID   22139183.
  9. ↑ Wilcke M, Johannes L, Galli T, Mayau V, Goud B, Salamero J (Dec 2000). "Rab11 regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-golgi network". The Journal of Cell Biology. 151 (6): 1207–20. doi:10.1083/jcb.151.6.1207. PMC   2190589 . PMID   11121436.
  10. ↑ Lai F, Stubbs L, Artzt K (Aug 1994). "Molecular analysis of mouse Rab11b: a new type of mammalian YPT/Rab protein". Genomics. 22 (3): 610–6. doi:10.1006/geno.1994.1434. PMID   8001972.
  11. ↑ Benli M, Döring F, Robinson DG, Yang X, Gallwitz D (Dec 1996). "Two GTPase isoforms, Ypt31p and Ypt32p, are essential for Golgi function in yeast". The EMBO Journal. 15 (23): 6460–75. doi:10.1002/j.1460-2075.1996.tb01037.x. PMC   452471 . PMID   8978673.
  12. ↑ Jedd G, Mulholland J, Segev N (May 1997). "Two new Ypt GTPases are required for exit from the yeast trans-Golgi compartment". The Journal of Cell Biology. 137 (3): 563–80. doi:10.1083/jcb.137.3.563. PMC   2139891 . PMID   9151665.
  13. 1 2 Lapierre LA, Dorn MC, Zimmerman CF, Navarre J, Burnette JO, Goldenring JR (Nov 2003). "Rab11b resides in a vesicular compartment distinct from Rab11a in parietal cells and other epithelial cells". Experimental Cell Research. 290 (2): 322–31. doi:10.1016/s0014-4827(03)00340-9. PMID   14567990.
  14. ↑ Chen W, Feng Y, Chen D, Wandinger-Ness A (Nov 1998). "Rab11 is required for trans-golgi network-to-plasma membrane transport and a preferential target for GDP dissociation inhibitor". Molecular Biology of the Cell. 9 (11): 3241–57. doi:10.1091/mbc.9.11.3241. PMC   25617 . PMID   9802909.
  15. ↑ Cox D, Lee DJ, Dale BM, Calafat J, Greenberg S (Jan 2000). "A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis". Proceedings of the National Academy of Sciences of the United States of America. 97 (2): 680–5. Bibcode:2000PNAS...97..680C. doi: 10.1073/pnas.97.2.680 . PMC   15390 . PMID   10639139.
  16. 1 2 3 4 5 6 Scapin SM, Carneiro FR, Alves AC, Medrano FJ, Guimarães BG, Zanchin NI (Jun 2006). "The crystal structure of the small GTPase Rab11b reveals critical differences relative to the Rab11a isoform". Journal of Structural Biology. 154 (3): 260–8. doi:10.1016/j.jsb.2006.01.007. PMID   16545962.
  17. ↑ Ullrich O, Reinsch S, Urbé S, Zerial M, Parton RG (Nov 1996). "Rab11 regulates recycling through the pericentriolar recycling endosome". The Journal of Cell Biology. 135 (4): 913–24. doi:10.1083/jcb.135.4.913. PMC   2133374 . PMID   8922376.
  18. ↑ Wang X, Kumar R, Navarre J, Casanova JE, Goldenring JR (Sep 2000). "Regulation of vesicle trafficking in madin-darby canine kidney cells by Rab11a and Rab25". The Journal of Biological Chemistry. 275 (37): 29138–46. doi: 10.1074/jbc.M004410200 . PMID   10869360.
  19. 1 2 Schlierf B, Fey GH, Hauber J, Hocke GM, Rosorius O (Aug 2000). "Rab11b is essential for recycling of transferrin to the plasma membrane". Experimental Cell Research. 259 (1): 257–65. doi:10.1006/excr.2000.4947. PMID   10942597.
  20. ↑ Shiba T, Koga H, Shin HW, Kawasaki M, Kato R, Nakayama K, Wakatsuki S (Oct 2006). "Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1". Proceedings of the National Academy of Sciences of the United States of America. 103 (42): 15416–21. Bibcode:2006PNAS..10315416S. doi: 10.1073/pnas.0605357103 . PMC   1622838 . PMID   17030804.
  21. ↑ Pasqualato S, Senic-Matuglia F, Renault L, Goud B, Salamero J, Cherfils J (Mar 2004). "The structural GDP/GTP cycle of Rab11 reveals a novel interface involved in the dynamics of recycling endosomes". The Journal of Biological Chemistry. 279 (12): 11480–8. doi: 10.1074/jbc.M310558200 . PMID   14699104.
  22. ↑ Greenfield JP, Leung LW, Cai D, Kaasik K, Gross RS, Rodriguez-Boulan E, Greengard P, Xu H (Apr 2002). "Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesis". The Journal of Biological Chemistry. 277 (14): 12128–36. doi: 10.1074/jbc.M110009200 . PMID   11823458.
  23. ↑ Dumanchin C, Czech C, Campion D, Cuif MH, Poyot T, Martin C, Charbonnier F, Goud B, Pradier L, Frebourg T (Jul 1999). "Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport". Human Molecular Genetics. 8 (7): 1263–9. doi: 10.1093/hmg/8.7.1263 . PMID   10369872.
  24. ↑ Cullinane AR, Straatman-Iwanowska A, Zaucker A, Wakabayashi Y, Bruce CK, Luo G, Rahman F, Gürakan F, Utine E, Ozkan TB, Denecke J, Vukovic J, Di Rocco M, Mandel H, Cangul H, Matthews RP, Thomas SG, Rappoport JZ, Arias IM, Wolburg H, Knisely AS, Kelly DA, Müller F, Maher ER, Gissen P (Apr 2010). "Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization". Nature Genetics. 42 (4): 303–12. doi:10.1038/ng.538. PMC   5308204 . PMID   20190753.
  25. ↑ Luiro K, Yliannala K, Ahtiainen L, Maunu H, Järvelä I, Kyttälä A, Jalanko A (Dec 2004). "Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway". Human Molecular Genetics. 13 (23): 3017–27. doi: 10.1093/hmg/ddh321 . PMID   15471887.
  26. ↑ Stendel C, Roos A, Kleine H, Arnaud E, Ozçelik M, Sidiropoulos PN, Zenker J, Schüpfer F, Lehmann U, Sobota RM, Litchfield DW, Lüscher B, Chrast R, Suter U, Senderek J (Aug 2010). "SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling". Brain. 133 (Pt 8): 2462–74. doi: 10.1093/brain/awq168 . PMID   20826437.
  27. ↑ Cortes C, Rzomp KA, Tvinnereim A, Scidmore MA, Wizel B (Dec 2007). "Chlamydia pneumoniae inclusion membrane protein Cpn0585 interacts with multiple Rab GTPases". Infection and Immunity. 75 (12): 5586–96. doi:10.1128/IAI.01020-07. PMC   2168330 . PMID   17908815.
  28. ↑ Rejman Lipinski A, Heymann J, Meissner C, Karlas A, Brinkmann V, Meyer TF, Heuer D (Oct 2009). "Rab6 and Rab11 regulate Chlamydia trachomatis development and golgin-84-dependent Golgi fragmentation". PLOS Pathogens. 5 (10): e1000615. doi: 10.1371/journal.ppat.1000615 . PMC   2752117 . PMID   19816566.
  29. ↑ Rzomp KA, Scholtes LD, Briggs BJ, Whittaker GR, Scidmore MA (Oct 2003). "Rab GTPases are recruited to chlamydial inclusions in both a species-dependent and species-independent manner". Infection and Immunity. 71 (10): 5855–70. doi:10.1128/IAI.71.10.5855-5870.2003. PMC   201052 . PMID   14500507.
  30. ↑ Amorim MJ, Bruce EA, Read EK, Foeglein A, Mahen R, Stuart AD, Digard P (May 2011). "A Rab11- and microtubule-dependent mechanism for cytoplasmic transport of influenza A virus viral RNA". Journal of Virology. 85 (9): 4143–56. doi:10.1128/JVI.02606-10. PMC   3126276 . PMID   21307188.
  31. ↑ Bruce EA, Digard P, Stuart AD (Jun 2010). "The Rab11 pathway is required for influenza A virus budding and filament formation". Journal of Virology. 84 (12): 5848–59. doi:10.1128/JVI.00307-10. PMC   2876627 . PMID   20357086.
  32. ↑ Momose F, Sekimoto T, Ohkura T, Jo S, Kawaguchi A, Nagata K, Morikawa Y (2011-06-22). "Apical transport of influenza A virus ribonucleoprotein requires Rab11-positive recycling endosome". PLOS ONE. 6 (6): e21123. Bibcode:2011PLoSO...621123M. doi: 10.1371/journal.pone.0021123 . PMC   3120830 . PMID   21731653.
  33. ↑ Rowe, Regina K.; Jason W. Suszko; Andrew Pekosz (2008-12-20). "Roles for the recycling endosome, Rab8, and Rab11 in hantavirus release from epithelial cells". Virology. 382 (2): 239–249. doi:10.1016/j.virol.2008.09.021. ISSN   0042-6822. PMC   2648827 . PMID   18951604.

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