Abstract
Background
Planar cell polarity (PCP) is a phenomenon in which epithelial cells are polarized along the plane of a tissue. PCP is critical for a variety of developmental processes and is regulated by a set of evolutionarily conserved PCP signaling proteins. Many of the PCP proteins adopt characteristic asymmetric localizations on the opposing cellular boundaries. Currently, the molecular mechanisms that establish and maintain this PCP asymmetry remain largely unclear. Newly synthesized integral PCP proteins are transported along the secretory transport pathway to the plasma membranes. Once delivered to the plasma membranes, PCP proteins undergo endocytosis. Recent studies reveal insights into the intracellular trafficking of PCP proteins, suggesting that intracellular trafficking of PCP proteins contributes to establishing the PCP asymmetry.
Objective
To understand the intracellular trafficking of planar cell polarity proteins in the secretory transport pathway and endocytic transport pathway.
Methods
This review summarizes our current understanding of the intracellular trafficking of PCP proteins. We highlights the molecular mechanisms that regulate sorting of PCP proteins into transport vesicles and how the intracellular trafficking process regulates the asymmetric localizations of PCP proteins.
Results
Current studies reveal novel insights into the molecular mechanisms mediating intracellular trafficking of PCP proteins. This process is critical for delivering newly synthesized PCP proteins to their specific destinations, removing the unstable or mislocalized PCP proteins from the plasma membranes and preserving tissue polarity during proliferation of mammalian skin cells.
Conclusion
Understanding how PCP proteins are delivered in the secretory and endocytic transport pathway will provide mechanistic insights into how the asymmetric localizations of PCP proteins are established and maintained.
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References
Adler P N, Zhu C, Stone D (2004). Inturned localizes to the proximal side of wing cells under the instruction of upstream planar polarity proteins. Curr Biol, 14(22): 2046–2051
Aigouy B, Farhadifar R, Staple D B, Sagner A, Röper J C, Jülicher F, Eaton S (2010). Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell, 142(5): 773–786
Ambegaonkar A A, Pan G, Mani M, Feng Y, Irvine K D (2012). Propagation of Dachsous-Fat planar cell polarity. Curr Biol, 22(14): 1302–1308
Angers S, Thorpe C J, Biechele T L, Goldenberg S J, Zheng N, MacCoss M J, Moon R T (2006). The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. Nat Cell Biol, 8(4): 348–357
Axelrod J D (2001). Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev, 15(10): 1182–1187
Bastock R, Strutt H, Strutt D (2003). Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development, 130(13): 3007–3014
Bayly R, Axelrod J D (2011). Pointing in the right direction: new developments in the field of planar cell polarity. Nat Rev Genet, 12 (6): 385–391
Bellaïche Y, Beaudoin-Massiani O, Stuttem I, Schweisguth F (2004). The planar cell polarity protein Strabismus promotes Pins anterior localization during asymmetric division of sensory organ precursor cells in Drosophila. Development, 131(2): 469–478
Brittle A, Thomas C, Strutt D (2012). Planar polarity specification through asymmetric subcellular localization of Fat and Dachsous. Curr Biol, 22(10): 907–914
Carvajal-Gonzalez J M, Balmer S, Mendoza M, Dussert A, Collu G, Roman A C, Weber U, Ciruna B, Mlodzik M (2015). The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo. Nat Commun, 6(1): 6751
Chen W, Hu L A, Semenov M V, Yanagawa S, Kikuchi A, Lefkowitz R J, Miller W E (2001). beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. Proc Natl Acad Sci USA, 98(26): 14889–14894
Chen W, ten Berge D, Brown J, Ahn S, Hu L A, Miller WE, Caron MG, Barak L S, Nusse R, Lefkowitz R J (2003). Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science, 301(5638): 1391–1394
Chen W S, Antic D, Matis M, Logan C Y, Povelones M, Anderson G A, Nusse R, Axelrod J D (2008). Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling. Cell, 133(6): 1093–1105
Cho B, Pierre-Louis G, Sagner A, Eaton S, Axelrod J D (2015). Clustering and negative feedback by endocytosis in planar cell polarity signaling is modulated by ubiquitinylation of prickle. PLoS Genet, 11(5): e1005259
Classen A K, Anderson K I, Marois E, Eaton S (2005). Hexagonal packing of Drosophila wing epithelial cells by the planar cell polarity pathway. Dev Cell, 9(6): 805–817
Devenport D (2014). The cell biology of planar cell polarity. J Cell Biol, 207(2): 171–179
Devenport D, Fuchs E (2008). Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol, 10(11): 1257–1268
Devenport D, Oristian D, Heller E, Fuchs E (2011). Mitotic internalization of planar cell polarity proteins preserves tissue polarity. Nat Cell Biol, 13(8): 893–902
Donaldson J G, Jackson C L (2011). ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol, 12(6): 362–375
Feiguin F, Hannus M, Mlodzik M, Eaton S (2001). The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. Dev Cell, 1(1): 93–101
Gault W J, Olguin P, Weber U, Mlodzik M (2012). Drosophila CK1-g, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking. J Cell Biol, 196(5): 605–621
Gho M, Schweisguth F (1998). Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature, 393(6681): 178–181
Gillingham A K, Munro S (2007). The small G proteins of the Arf family and their regulators. Annu Rev Cell Dev Biol, 23(1): 579–611
Guo Y, Sirkis D W, Schekman R (2014). Protein sorting at the trans- Golgi network. Annu Rev Cell Dev Biol, 30(1): 169–206
Guo Y, Zanetti G, Schekman R (2013). A novel GTP-binding proteinadaptor protein complex responsible for export of Vangl2 from the trans Golgi network. Elife, 2: e00160
Harumoto T, Ito M, Shimada Y, Kobayashi T J, Ueda H R, Lu B, Uemura T (2010). Atypical cadherins Dachsous and Fat control dynamics of noncentrosomal microtubules in planar cell polarity. Dev Cell, 19(3): 389–401
Heck B W, Devenport D (2017). Trans-endocytosis of planar cell polarity complexes during cell division. Curr Biol, 27: 3725–3733
Heldwein E E, Macia E, Wang J, Yin H L, Kirchhausen T, Harrison S C (2004). Crystal structure of the clathrin adaptor protein 1 core. Proc Natl Acad Sci USA, 101(39): 14108–14113
Hirst J, Motley A, Harasaki K, Peak Chew S Y, Robinson M S (2003). EpsinR: an ENTH domain-containing protein that interacts with AP- 1. Mol Biol Cell, 14(2): 625–641
Kibar Z, Underhill D A, Canonne-Hergaux F, Gauthier S, Justice M J, Gros P (2001a). Identification of a new chemically induced allele (Lp (m1Jus)) at the loop-tail locus: morphology, histology, and genetic mapping. Genomics, 72(3): 331–337
Kibar Z, Vogan K J, Groulx N, Justice M J, Underhill D A, Gros P (2001b). Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. Nat Genet, 28(3): 251–255
Kim G H, Her J H, Han J K (2008). Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements. J Cell Biol, 182(6): 1073–1082
Klein T J, Mlodzik M (2005). Planar cell polarization: an emerging model points in the right direction. Annu Rev Cell Dev Biol, 21(1): 155–176
Lee I, Doray B, Govero J, Kornfeld S (2008). Binding of cargo sorting signals to AP-1 enhances its association with ADP ribosylation factor 1-GTP. J Cell Biol, 180(3): 467–472
Lee J H, Fischer J A (2012). Drosophila Tel2 is expressed as a translational fusion with EpsinR and is a regulator of wingless signaling. PLoS One, 7(9): e46357
Lee J H, Overstreet E, Fitch E, Fleenor S, Fischer J A (2009). Drosophila liquid facets-Related encodes Golgi epsin and is an essential gene required for cell proliferation, growth, and patterning. Dev Biol, 331 (1): 1–13
Lee M C, Miller E A, Goldberg J, Orci L, Schekman R (2004). Bidirectional protein transport between the ER and Golgi. Annu Rev Cell Dev Biol, 20(1): 87–123
Lu B, Usui T, Uemura T, Jan L, Jan Y N (1999). Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila. Curr Biol, 9(21): 1247–1250
Ma T, Li B, Wang R, Lau P K, Huang Y, Jiang L, Schekman R, Guo Y (2018). A mechanism for differential sorting of the planar cell polarity proteins Frizzled6 and Vangl2 at the trans-Golgi network. J Biol Chem, 293(22): 8410–8427
Matakatsu H, Blair S S (2004). Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing. Development, 131(15): 3785–3794
Merte J, Jensen D, Wright K, Sarsfield S, Wang Y, Schekman R, Ginty D D (2010). Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. Nat Cell Biol, 12:41–46; sup pp 41–48
Mottola G, Classen A K, González-Gaitán M, Eaton S, Zerial M (2010). A novel function for the Rab5 effector Rabenosyn-5 in planar cell polarity. Development, 137(14): 2353–2364
Mukai A, Yamamoto-Hino M, Awano W, Watanabe W, Komada M, Goto S (2010). Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J, 29 (13): 2114–2125
Murdoch J N, Doudney K, Paternotte C, Copp A J, Stanier P (2001). Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification. Hum Mol Genet, 10(22): 2593–2601
Narimatsu M, Bose R, Pye M, Zhang L, Miller B, Ching P, Sakuma R, Luga V, Roncari L, Attisano L, Wrana J L (2009). Regulation of planar cell polarity by Smurf ubiquitin ligases. Cell, 137(2): 295–307
Olofsson J, Sharp K A, Matis M, Cho B, Axelrod J D (2014). Prickle/spiny-legs isoforms control the polarity of the apical microtubule network in planar cell polarity. Development, 141(14): 2866–2874
Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, De Robertis E M (1999). The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature, 397(6721): 707–710
Ren X, Farías G G, Canagarajah B J, Bonifacino J S, Hurley J H (2013). Structural basis for recruitment and activation of the AP-1 clathrin adaptor complex by Arf1. Cell, 152(4): 755–767
Sepich D S, Usmani M, Pawlicki S, Solnica-Krezel L (2011). Wnt/PCP signaling controls intracellular position of MTOCs during gastrulation convergence and extension movements. Development, 138(3): 543–552
Shi D, Usami F, Komatsu K, Oka S, Abe T, Uemura T, Fujimori T (2016). Dynamics of planar cell polarity protein Vangl2 in the mouse oviduct epithelium. Mech Dev, 141: 78–89
Shimada Y, Yonemura S, Ohkura H, Strutt D, Uemura T (2006). Polarized transport of Frizzled along the planar microtubule arrays in Drosophila wing epithelium. Dev Cell, 10(2): 209–222
Shrestha R, Little K A, Tamayo J V, Li W, Perlman D H, Devenport D (2015). Mitotic Control of Planar Cell Polarity by Polo-like Kinase 1. Dev Cell, 33(5): 522–534
Strutt D, Warrington S J (2008). Planar polarity genes in the Drosophila wing regulate the localisation of the FH3-domain protein Multiple Wing Hairs to control the site of hair production. Development, 135 (18): 3103–3111
Strutt D I (2001). Asymmetric localization of frizzled and the establishment of cell polarity in the Drosophila wing. Mol Cell, 7 (2): 367–375
Strutt H, Searle E, Thomas-Macarthur V, Brookfield R, Strutt D (2013a). A Cul-3-BTB ubiquitylation pathway regulates junctional levels and asymmetry of core planar polarity proteins. Development, 140(8): 1693–1702
Strutt H, Strutt D (2008). Differential stability of flamingo protein complexes underlies the establishment of planar polarity. Curr Biol, 18(20): 1555–1564
Strutt H, Thomas-MacArthur V, Strutt D (2013b). Strabismus promotes recruitment and degradation of farnesylated prickle in Drosophila melanogaster planar polarity specification. PLoS Genet, 9(7): e1003654
Strutt H, Warrington S J, Strutt D (2011). Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains. Dev Cell, 20(4): 511–525
Tauriello D V, Haegebarth A, Kuper I, Edelmann M J, Henraat M, Canninga-van Dijk M R, Kessler B M, Clevers H, Maurice M M (2010). Loss of the tumor suppressor CYLD enhances Wnt/betacatenin signaling through K63-linked ubiquitination of Dvl. Mol Cell, 37(5): 607–619
Tree D R, Shulman J M, Rousset R, Scott M P, Gubb D, Axelrod J D (2002). Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell, 109(3): 371–381
Vladar E K, Bayly R D, Sangoram A M, Scott M P, Axelrod J D (2012). Microtubules enable the planar cell polarity of airway cilia. Curr Biol, 22(23): 2203–2212
Wootton R J (1992). Functional morphology of insect wings. Annu Rev Entomol, 37(1): 113–140
Yamamoto A, Nagano T, Takehara S, Hibi M, Aizawa S (2005). Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF. Cell, 120(2): 223–235
Yu A, Rual J F, Tamai K, Harada Y, Vidal M, He X, Kirchhausen T (2007). Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling. Dev Cell, 12(1): 129–141
Acknowledgments
This work was supported by the Hong Kong Research Grants Council Grants 26100315, 16101116, AoE/M-05/12-3, C4002-17G to Y.G.
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Huang, Y., Ma, T. & Guo, Y. Intracellular trafficking of planar cell polarity proteins. Front. Biol. 13, 395–405 (2018). https://doi.org/10.1007/s11515-018-1520-4
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DOI: https://doi.org/10.1007/s11515-018-1520-4