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]


Related Research Articles

<span class="mw-page-title-main">Cilium</span> Organelle found on eukaryotic cells

The cilium, is a membrane-bound organelle found on most types of eukaryotic cell. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projection that extends from the surface of the much larger cell body. Eukaryotic flagella found on sperm cells and many protozoans have a similar structure to motile cilia that enables swimming through liquids; they are longer than cilia and have a different undulating motion.

<span class="mw-page-title-main">Basal body</span> Protein structure found at the base of cilium or flagellum).

A basal body is a protein structure found at the base of a eukaryotic undulipodium. The basal body was named by Theodor Wilhelm Engelmann in 1880. It is formed from a centriole and several additional protein structures, and is, essentially, a modified centriole. The basal body serves as a nucleation site for the growth of the axoneme microtubules. Centrioles, from which basal bodies are derived, act as anchoring sites for proteins that in turn anchor microtubules, and are known as the microtubule organizing center (MTOC). These microtubules provide structure and facilitate movement of vesicles and organelles within many eukaryotic cells.

<span class="mw-page-title-main">Phragmoplast</span> Structure in dividing plant cells that builds the daughter cell wall

The phragmoplast is a plant cell specific structure that forms during late cytokinesis. It serves as a scaffold for cell plate assembly and subsequent formation of a new cell wall separating the two daughter cells. The phragmoplast can only be observed in Phragmoplastophyta, a clade that includes the Coleochaetophyceae, Zygnematophyceae, Mesotaeniaceae, and Embryophyta. Some algae use another type of microtubule array, a phycoplast, during cytokinesis.

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

Intraflagellar transport (IFT) is a bidirectional motility along axoneme microtubules that is essential for the formation (ciliogenesis) and maintenance of most eukaryotic cilia and flagella. It is thought to be required to build all cilia that assemble within a membrane projection from the cell surface. Plasmodium falciparum cilia and the sperm flagella of Drosophila are examples of cilia that assemble in the cytoplasm and do not require IFT. The process of IFT involves movement of large protein complexes called IFT particles or trains from the cell body to the ciliary tip and followed by their return to the cell body. The outward or anterograde movement is powered by kinesin-2 while the inward or retrograde movement is powered by cytoplasmic dynein 2/1b. The IFT particles are composed of about 20 proteins organized in two subcomplexes called complex A and B.

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

Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).

<span class="mw-page-title-main">Polycystin 1</span> Family of transport proteins

Polycystin 1 (PC1) is a protein that in humans is encoded by the PKD1 gene. Mutations of PKD1 are associated with most cases of autosomal dominant polycystic kidney disease, a severe hereditary disorder of the kidneys characterised by the development of renal cysts and severe kidney dysfunction.

<span class="mw-page-title-main">Polycystin 2</span> Protein and coding gene in humans

Polycystin-2(PC2) is a protein that in humans is encoded by the PKD2 gene.

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

Periplakin is a protein that in humans is encoded by the PPL gene.

<span class="mw-page-title-main">KLC1</span> Gene of the kinesin light chain family

Kinesin light chain 1 is a protein that in humans is encoded by the KLC1 gene.

<span class="mw-page-title-main">CEP290</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein of 290 kDa is a protein that in humans is encoded by the CEP290 gene. CEP290 is located on the Q arm of chromosome 12.

<span class="mw-page-title-main">Kinesin-like protein KIF3A</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF3A is a protein that in humans is encoded by the KIF3A gene.

<span class="mw-page-title-main">PKD2L1</span> Protein-coding gene in the species Homo sapiens

Polycystic kidney disease 2-like 1 protein also known as transient receptor potential polycystic 2 is a protein that in humans is encoded by the PKD2L1 gene.

<span class="mw-page-title-main">MAGI3</span> Protein-coding gene in the species Homo sapiens

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 is an enzyme that in humans is encoded by the MAGI3 gene.

<span class="mw-page-title-main">KIF17</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF17 is a protein that in humans is encoded by the KIF17 gene. KIF17 and its close relative, C. elegans OSM-3, are members of the kinesin-2 family of plus-end directed microtubule-based motor proteins. In contrast to heterotrimeric kinesin-2 motors, however, KIF17 and OSM-3 form distinct homodimeric complexes. Homodimeric kinesin-2 has been implicated in the transport of NMDA receptors along dendrites for delivery to the dendritic membrane, whereas both heterotrimeric and homodimeric kinesin-2 motors function cooperatively in anterograde intraflagellar transport (IFT) and cilium biogenesis.

<span class="mw-page-title-main">IFT20</span> Protein-coding gene in the species Homo sapiens

Intraflagellar transport protein 20 homolog is a protein that in humans is encoded by the IFT20 gene. The gene is composed of 6 exons and is located on human chromosome 17p11.1. This gene is expressed in human brain, lung, kidney and pancreas, and lower expression were also detected in human placenta, liver, thymus, prostate and testis.

<span class="mw-page-title-main">Ciliopathy</span> Genetic disease resulting in abnormal formation or function of cilia

A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while an embryo is developing can lead to a set of malformations that can occur regardless of the particular genetic problem. The similarity of the clinical features of these developmental disorders means that they form a recognizable cluster of syndromes, loosely attributed to abnormal ciliary function and hence called ciliopathies. Regardless of the actual genetic cause, it is clustering of a set of characteristic physiological features which define whether a syndrome is a ciliopathy.

RPGRIP1L is a human gene.

Ciliogenesis is defined as the building of the cell's antenna or extracellular fluid mediation mechanism. It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organelles of cells and are involved in numerous activities such as cell signaling, processing developmental signals, and directing the flow of fluids such as mucus over and around cells. Due to the importance of these cell processes, defects in ciliogenesis can lead to numerous human diseases related to non-functioning cilia. Ciliogenesis may also play a role in the development of left/right handedness in humans.

The Polycystin Cation Channel (PCC) Family consists of several transporters ranging in size from 500 to over 4000 amino acyl residues (aas) in length and exhibiting between 5 and 18 transmembrane segments (TMSs). This family is a constituent of the Voltage-Gated Ion Channel (VIC) Superfamily. These transporters generally catalyze the export of cations. A representative list of proteins belonging to the PCC family can be found in the Transporter Classification Database.

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

Giantin or Golgin subfamily B member 1 is a protein that in humans is encoded by the GOLGB1 gene. Giantin is located at the cis-medial rims of the Golgi apparatus and is part of the Golgi matrix that is responsible for membrane trafficking in secretory pathway of proteins. This function is key for proper localisation of proteins at the plasma membrane and outside the cell which is important for cell function that is dependent on for example receptors and the extracellular matrix function. Recent animal model knockout studies of GOLGB1 in mice, rat, and zebrafish have shown that phenotypes are different between species ranging from mild to severe craniofacial defects in the rodent models to just minor size defects in zebrafish. However, in adult zebrafish a tumoral calcinosis-like phenotype was observed, and in humans such phenotype has been linked to defective glycosyltransferase function.

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. Academic Press. 85: 271.
  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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