RAB11FIP5

Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.[5][6][7]

RAB11FIP5
Identifiers
AliasesRAB11FIP5, GAF1, RIP11, pp75, RAB11 family interacting protein 5, rab11-FIP5, gaf-1
External IDsOMIM: 605536 MGI: 1098586 HomoloGene: 9158 GeneCards: RAB11FIP5
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2p13.2Start73,073,382 bp[1]
End73,156,721 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

26056

52055

Ensembl

ENSG00000135631

ENSMUSG00000051343

UniProt

Q9BXF6

Q8R361

RefSeq (mRNA)

NM_015470
NM_001371272

NM_001003955
NM_177466

RefSeq (protein)

NP_056285
NP_001358201

NP_001003955
NP_803417

Location (UCSC)Chr 2: 73.07 – 73.16 MbChr 6: 85.33 – 85.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Interactions

RAB11FIP5 has been shown to interact with RAB11A[6][8][9] and RAB25.[8][9]

Vesicle trafficking

Rab11FIP5 is one of the many proteins that have been shown to interact with the Rab11 protein.[8] Rab GTPases, such as Rab11, are enzymes that are involved in vesicular trafficking. Rab11 specifically plays a key role in endocytic trafficking and recycling through guiding early endosomes to endosome recycling complexes.[10] Rab11FIP5, like most other Rab11FIP proteins, interacts with Rab11 by serving as an adaptor protein. This leads to downstream changes with regards to which proteins can interact. This is a result of the various Rab11FIP proteins that each have different binding partners. This process allows for the coordination and organization of endosomal transport and ultimately gives Rab11 its versatile function in the cell.[10] It is believed that Rab11 recruits specific Rab11FIP proteins to the surface of vesicles in order to determine how the vesicle will behave.[11]

Studies have shown that Rab11FIP5 localizes to the perinuclear endosomes where it aids in sorting vesicles into the slow recycling route.[11] This process involves the transport of cargo proteins, like endocytosed receptors, to endosome recycling complexes and subsequently to the plasma membrane. This is in contrast to the fast constitutive recycling route which allows for the direct transport of cargo from the endosome to the plasma membrane.[11] Rab11FIP5 aids in this sorting process by binding to kinesin II and forming a protein complex to regulate vesicular trafficking. Some of the proteins that are regulated through Rab11FIP5 mediated vesicle trafficking are microtubule proteins and the TfR receptor. This links Rab11FIP5 functionality to the cell cytoskeleton and the iron uptake of a cell, respectively.[11]

Other functions

Rab11FIP5 has been shown to play a role in the nervous system because it functions in neurons. Studies have suggested that Rab11FIP5 is involved in regulating the localization of the postsynaptic AMPA-type glutamate receptor. The AMPA receptor is an excitatory receptor that can be found on the plasma membranes of neurons. Studies have shown that mice with the Rab11FIP5 gene knocked out have severe long term neuronal depression. Without the presence of Rab11FIP5, it is hypothesized that the internalized AMPA receptors cannot be recycled back onto the plasma membrane because the receptors cannot be correctly trafficked to intracellular organelles responsible for recycling.[12]

Rab11FIP5 has also been implicated as a protein involved in the creation of tissue polarity during development. Rab11FIP5 has been shown to be involved in the vesicle trafficking and degradation of proteins used to coordinate embryonic development. This is conducted in a manner that helps maintain the ectoderm polarity in embryonic Drosophila.[13]

Rab11FIP5 is also suggested to be involved in aiding salivary epithelial cells to adjust to extracellular pH. V-ATPase, a proton pump protein, has been shown to be reliant on Rab11FIP5 mediated vesicle trafficking. When Rab11FIP5 is knocked down, salivary cells cannot correctly translocate V-ATPase to the plasma membrane in response to extracellular acidosis. While this pathway remains largely unknown, these results suggest a link between Rab11FIP5 function and the maintenance of the buffering capacity of saliva.[14]

Rab11FIP5 is also required for regulated exocytosis in neuroendocrine cells. Knockdown of Rab11FIP5 inhibited calcium-stimulated dense core vesicle (DCV) exocytosis in a neuroendocrine cell line BON cells. DCV membrane proteins are lost to the plasma membrane during exocytosis and recycle to the Golgi through the retrograde trafficking pathway. The requirement of Rab11FIP5 for regulated DCV exocytosis may be attributed to its role in endosome-mediated retrograde trafficking.[15]

References
  1. GRCh38: Ensembl release 89: ENSG00000135631 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000051343 - 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. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (December 1998). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
  6. Prekeris R, Klumperman J, Scheller RH (December 2000). "A Rab11/Rip11 protein complex regulates apical membrane trafficking via recycling endosomes". Molecular Cell. 6 (6): 1437–48. doi:10.1016/S1097-2765(00)00140-4. PMID 11163216.
  7. "Entrez Gene: RAB11FIP5 RAB11 family interacting protein 5 (class I)".
  8. Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR (October 2001). "Identification and characterization of a family of Rab11-interacting proteins". The Journal of Biological Chemistry. 276 (42): 39067–75. doi:10.1074/jbc.M104831200. PMID 11495908.
  9. Prekeris R, Davies JM, Scheller RH (October 2001). "Identification of a novel Rab11/25 binding domain present in Eferin and Rip proteins". The Journal of Biological Chemistry. 276 (42): 38966–70. doi:10.1074/jbc.M106133200. PMID 11481332.
  10. Grant BD, Donaldson JG (2009). "Pathways and mechanisms of endocytic recycling". Nature Reviews Molecular Cell Biology. 10 (9): 597–608. doi:10.1038/nrm2755. PMC 3038567. PMID 19696797.
  11. Schonteich E, Wilson GM, Burden J, Hopkins CR, Anderson K, Goldenring JR, Prekeris R (November 2008). "The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling". Journal of Cell Science. 121 (Pt 22): 3824–33. doi:10.1242/jcs.032441. PMC 4365997. PMID 18957512.
  12. Bacaj T, Ahmad M, Jurado S, Malenka RC, Südhof TC (May 2015). "Synaptic Function of Rab11Fip5: Selective Requirement for Hippocampal Long-Term Depression". The Journal of Neuroscience. 35 (19): 7460–74. doi:10.1523/JNEUROSCI.1581-14.2015. PMC 4429152. PMID 25972173.
  13. Calero-Cuenca FJ, Sotillos S (September 2016). "Nuf and Rip11 requirement for polarity determinant recycling during Drosophila development". Small GTPases. 9 (4): 352–359. doi:10.1080/21541248.2016.1235386. PMC 5997155. PMID 27687567.
  14. Oehlke O, Martin HW, Osterberg N, Roussa E (March 2011). "Rab11b and its effector Rip11 regulate the acidosis-induced traffic of V-ATPase in salivary ducts". Journal of Cellular Physiology. 226 (3): 638–51. doi:10.1002/jcp.22388. PMID 20717956. S2CID 10428914.
  15. Zhang X, Jiang S, Mitok KA, Li L, Attie AD, Martin TFJ (July 2017). "BAIAP3, a C2 domain-containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells". The Journal of Cell Biology. 216 (7): 2151–2166. doi:10.1083/jcb.201702099. PMC 5496627. PMID 28626000.

Further reading
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