RVxP motif

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RVxP motif is a protein motif involved in localizing proteins into cilia.

Cilia are sensory organelle of cells, whose malfunction can cause diseases such as polycystic kidney disease, [1] nephronophthisis and Bardet-Biedl syndrome. Proteins employed in the cilia are targeted there when they bear specific entry signals, whereas proteins not situated in cilia are removed or prevented from entering the organelles. [2] Entry signals have been found in ciliary/flagellar proteins of the protozoans Leishmania and Trypanosoma . [3]

The RVxP motif was first described for the PKD2 protein [4] and when inserted in the transferrin receptor it can target it to cilia. [5] It probably carries out its signal function through protein interactions [3] although the exact process [6] and where in the cell it takes place are unknown. [7] Three candidate proteins involved in "receiving" this signal are pericentrin at the basal body of cilia, intraflagellar transport proteins such as IFT57 [3] and ARF4 [8] while the BBSome does not appear to interact with the sequence. [9] The kinesins KIF17 is implicated in transporting the CNGB1 protein which has a RVxP motif into human cilia, [4] as is Rab8a in transporting PKD2. [5] Not all ciliary proteins use a RVxP motif for transport, however; [10] VxPx and Ax(S/A)xQ have also been described as cilium-targeting motifs. [6]

Examples of proteins with RVxP motifs associated with cilia:

Other proteins associated with cilia for which the occurrence of a RVxP motif has been discussed are PKD1 and PSEN2. [24]


References

  1. Geng et al. 2006, p. 1383.
  2. Geng et al. 2006, p. 1390.
  3. 1 2 3 4 Geng et al. 2006, p. 1391.
  4. 1 2 3 Jenkins et al. 2006, p. 1211.
  5. 1 2 Hoffmeister et al. 2011, p. 641.
  6. 1 2 Dishinger, John F.; Kee, Hooi Lynn; Jenkins, Paul M.; Fan, Shuling; Hurd, Toby W.; Hammond, Jennetta W.; Truong, Yen Nhu-Thi; Margolis, Ben; Martens, Jeffrey R.; Verhey, Kristen J. (July 2010). "Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-β2 and RanGTP". Nature Cell Biology. 12 (7): 709. doi:10.1038/ncb2073. ISSN   1476-4679. PMC   2896429 . PMID   20526328.
  7. Hoffmeister et al. 2011, p. 642.
  8. Ward, Heather H.; Brown-Glaberman, Ursa; Wang, Jing; Morita, Yoshiko; Alper, Seth L.; Bedrick, Edward J.; Gattone, Vincent H.; Deretic, Dusanka; Wandinger-Ness, Angela (20 July 2011). "A conserved signal and GTPase complex are required for the ciliary transport of polycystin-1". Molecular Biology of the Cell. 22 (18): 3298. doi: 10.1091/mbc.e11-01-0082 . ISSN   1059-1524. PMC   3172256 . PMID   21775626.
  9. Wingfield, Jenna L.; Lechtreck, Karl-Ferdinand; Lorentzen, Esben (2018-12-07). "Trafficking of ciliary membrane proteins by the intraflagellar transport/BBSome machinery". Essays in Biochemistry. 62 (6): 753–763. doi:10.1042/EBC20180030. ISSN   0071-1365. PMC   6737936 . PMID   30287585.
  10. Yoder, Bradley K. (1 May 2007). "Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease" . Journal of the American Society of Nephrology. 18 (5): 1383. doi: 10.1681/ASN.2006111215 . ISSN   1046-6673. PMID   17429051.
  11. Lancaster, Madeline A.; Schroth, Jana; Gleeson, Joseph G. (June 2011). "Subcellular spatial regulation of canonical Wnt signalling at the primary cilium". Nature Cell Biology. 13 (6): 703. doi:10.1038/ncb2259. ISSN   1476-4679. PMC   3107376 . PMID   21602792.
  12. Blacque, O.; Cevik, S.; Clarke, L.; Van Wijk, E.; Sanders, A.; Van Reeuwijk, J.; Boldt, K.; Ueffing, M.; Roepman, R.; Kremer, H. (16 November 2012). "Differential requirements of ciliogenic/ciliopathy module components in restricting Joubert syndrome-associated Arl13b to a C. elegans Inv-like ciliary compartment". Cilia. 1 (1): O8. doi: 10.1186/2046-2530-1-S1-O8 . ISSN   2046-2530. PMC   3555713 .
  13. Nozaki, Shohei; Katoh, Yohei; Terada, Masaya; Michisaka, Saki; Funabashi, Teruki; Takahashi, Senye; Kontani, Kenji; Nakayama, Kazuhisa (1 February 2017). "Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E". Journal of Cell Science. 130 (3): 563–576. doi: 10.1242/jcs.197004 . ISSN   0021-9533. PMID   27927754.
  14. Revenkova, Ekaterina; Liu, Qing; Gusella, G. Luca; Iomini, Carlo (1 May 2018). "The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane". Journal of Cell Science. 131 (9): 3. doi: 10.1242/jcs.212324 . ISSN   0021-9533. PMC   5992585 . PMID   29592971.
  15. Laird, Joseph G.; Pan, Yuan; Modestou, Modestos; Yamaguchi, David M.; Song, Hongman; Sokolov, Maxim; Baker, Sheila A. (December 2015). "Identification of a VxP Targeting Signal in the Flagellar Na /K -ATPase". Traffic. 16 (12): 1249. doi: 10.1111/tra.12332 . PMC   4715669 . PMID   26373354.
  16. Jenkins et al. 2006, p. 1213.
  17. Ou, Young; Zhang, Ying; Cheng, Min; Rattner, Jerome B.; Dobrinski, Ina; van der Hoorn, Frans A. (2012-11-21). "Targeting of CRMP-2 to the Primary Cilium Is Modulated by GSK-3β". PLOS ONE. 7 (11): e48773. Bibcode:2012PLoSO...748773O. doi: 10.1371/journal.pone.0048773 . ISSN   1932-6203. PMC   3504062 . PMID   23185275.
  18. Dacheux, Denis; Roger, Benoit; Bosc, Christophe; Landrein, Nicolas; Roche, Emmanuel; Chansel, Lucie; Trian, Thomas; Andrieux, Annie; Papaxanthos-Roche, Aline; Marthan, Roger; Robinson, Derrick R.; Bonhivers, Mélanie (1 April 2015). "Human FAM154A (SAXO1) is a microtubule-stabilizing protein specific to cilia and related structures". Journal of Cell Science. 128 (7): 1295. doi: 10.1242/jcs.155143 . ISSN   0021-9533. PMID   25673876.
  19. 1 2 Bell, Aaron J.; Guerra, Charles; Phung, Vincent; Nair, Saraswathy; Seetharam, Raviraja; Satir, Peter (August 2009). "GEF1 is a Ciliary Sec7 GEF of Tetrahymena thermophila". Cell Motility and the Cytoskeleton. 66 (8): 483–499. doi:10.1002/cm.20348. ISSN   0886-1544. PMC   2767173 . PMID   19267341.
  20. Christensen, Søren T.; Pedersen, Stine F.; Satir, Peter; Veland, Iben R.; Schneider, Linda (1 January 2008). "Chapter 10 The Primary Cilium Coordinates Signaling Pathways in Cell Cycle Control and Migration During Development and Tissue Repair" . Current Topics in Developmental Biology. 85. Academic Press: 271. doi:10.1016/S0070-2153(08)00810-7. ISBN   978-0-12-374453-1. PMID   19147009.
  21. Geng et al. 2006, p. 1389.
  22. Geng et al. 2006, p. 1393.
  23. McLaughlin, Susan (11 January 2017). "Evidence that polycystins are involved in Hydra cnidocyte discharge". Invertebrate Neuroscience. 17 (1): 4. doi:10.1007/s10158-016-0194-3. ISSN   1439-1104. PMID   28078622. S2CID   3674409.
  24. Pearring, Jillian N.; Agustin, Jovenal T. San; Lobanova, Ekaterina S.; Gabriel, Christopher J.; Lieu, Eric C.; Monis, William J.; Stuck, Michael W.; Strittmatter, Lara; Jaber, Samer M.; Arshavsky, Vadim Y.; Pazour, Gregory J. (14 April 2017). "Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration". PLOS Genetics. 13 (4): 2. doi: 10.1371/journal.pgen.1006740 . ISSN   1553-7404. PMC   5409180 . PMID   28410364.

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