Frizzled-4 C-terminus Distal to KTXXXW Motif is Essential for Normal Dishevelled Recruitment and Norrin-stimulated Activation of Lef/Tcf-dependent Transcriptional Activation

Alexander C. Bertalovitz; Milly S. Pau; Shujuan Gao; Craig C. Malbon; Hsien-yu Wang

doi:10.5334/1750-2187-11-1

Frizzled-4 C-terminus Distal to KTXXXW Motif is Essential for Normal Dishevelled Recruitment and Norrin-stimulated Activation of Lef/Tcf-dependent Transcriptional Activation

Journal of Molecular Signaling

Volume 11 (2016): Issue 1

By: Alexander C. Bertalovitz, Milly S. Pau, Shujuan Gao, Craig C. Malbon and Hsien-yu Wang

Open Access

|Feb 2016

Abstract

The carboxy (C)-termini of G protein coupled receptors (GPCR) dictate essential functions. The KTXXXW motif C-terminus of Frizzleds (FZD) has been implicated in recruitment of Dishevelled (DVL). Through study of FZD₄and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin.

References

Drake MT Shenoy SK Lefkowitz RJ Trafficking of G protein-coupled receptors Circ Res 2006 99 6 570 582 10.1161/01.RES.0000242563.47507.ce
Open DOI Search in Google Scholar Back to article
Bockaert J Marin P Dumuis A Fagni L The ‘magic tail’ of G protein-coupled receptors: an anchorage for functional protein networks FEBS Lett 2003 546 1 65 72 10.1016/S0014-5793(03)00453-8 Available at http://www.ncbi.nlm.nih.gov/pubmed/12829238
Open DOI Search in Google Scholar Back to article
Nie J Lewis DL The proximal and distal C-terminal tail domains of the CB1 cannabinoid receptor mediate G protein coupling Neuroscience 2001 107 1 161 167 10.1016/S0306-4522(01)00335-9 Available at http://www.ncbi.nlm.nih.gov/pubmed/11744255
Open DOI Search in Google Scholar Back to article
Ahn KH Nishiyama A Mierke DF Kendall DA Hydrophobic residues in helix 8 of cannabinoid receptor 1 are critical for structural and functional properties Biochemistry 2010 49 3 502 511 10.1021/bi901619r
Open DOI Search in Google Scholar Back to article
Swift S Leger AJ Talavera J Zhang L Bohm A Role of the PAR1 receptor 8th helix in signaling: the 7-8-1 receptor activation mechanism J Biol Chem 2006 281 7 4109 4116 10.1074/jbc.M509525200
Open DOI Search in Google Scholar Back to article
Wang C Wu H Katritch V Han GW Huang XP Structure of the human smoothened receptor bound to an antitumour agent Nature 2013 497 7449 338 343 10.1038/nature12167
Open DOI Search in Google Scholar Back to article
Rasmussen SG Choi HJ Rosenbaum DM Kobilka TS Thian FS Crystal structure of the human beta2 adrenergic G-protein-coupled receptor Nature 2007 450 7168 383 387 10.1038/nature06325
Open DOI Search in Google Scholar Back to article
Murakami M Kouyama T Crystal structure of squid rhodopsin Nature 2008 453 7193 363 367 10.1038/nature06925
Open DOI Search in Google Scholar Back to article
Punchihewa C Ferreira AM Cassell R Rodrigues P Fujii N Sequence requirement and subtype specificity in the high-affinity interaction between human frizzled and dishevelled proteins Protein Sci 2009 18 5 994 1002 10.1002/pro.109
Open DOI Search in Google Scholar Back to article
Lemma V D’Agostino M Caporaso MG Mallardo M Oliviero G A disorder- to-order structural transition in the COOH-tail of Fz4 determines misfolding of the L501fsX533-Fz4 mutant Sci Rep 2013 3 2659 10.1038/srep02659
Open DOI Search in Google Scholar Back to article
Umbhauer M Djiane A Goisset C Penzo-Mendez A Riou JF The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling EMBO J 2000 19 18 4944 4954 10.1093/emboj/19.18.4944
Open DOI Search in Google Scholar Back to article
Schweizer L Varmus H Wnt/Wingless signaling through beta-catenin requires the function of both LRP/Arrow and frizzled classes of receptors BMC Cell Biol 2003 4 4 10.1186/1471-2121-4-4
Open DOI Search in Google Scholar Back to article
Yu H Ye X Guo N Nathans J Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes Development 2012 139 23 4383 4394 10.1242/dev.083352
Open DOI Search in Google Scholar Back to article
Atwood BK Lopez J Wager-Miller J Mackie K Straiker A Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis BMC Genomics 2011 12 14 10.1186/1471-2164-12-14
Open DOI Search in Google Scholar Back to article
Xu Q Wang YS Dabdoub A Smallwood PM Williams J Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair Cell 2004 116 6 883 895 10.1016/S0092-8674(04)00216-8
Open DOI Search in Google Scholar Back to article
Smallwood PM Williams J Xu Q Leahy DJ Nathans J Mutational analysis of Norrin-Frizzled4 recognition Journal of Biological Chemistry 2007 282 6 4057 4068 10.1074/jbc.M609618200
Open DOI Search in Google Scholar Back to article
Lee YN Gao Y Wang HY Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, -2, and -3 Cell Signal 2008 20 2 443 452 10.1016/j.cellsig.2007.11.005
Open DOI Search in Google Scholar Back to article
Cong F Schweizer L Varmus H Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP Development 2004 131 20 5103 5115 10.1242/dev.01318
Open DOI Search in Google Scholar Back to article
Lu D Zhao Y Tawatao R Cottam HB Sen M Activation of the Wnt signaling pathway in chronic lymphocytic leukemia Proc Natl Acad Sci U S A 2004 101 9 3118 3123 10.1073/pnas.0308648100
Open DOI Search in Google Scholar Back to article
Binnerts ME Kim KA Bright JM Patel SM Tran K R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6 Proc Natl Acad Sci U S A 2007 104 37 14700 14705 10.1073/pnas.0702305104
Open DOI Search in Google Scholar Back to article
Gayen S Li Q Kim YM Kang C Structure of the C-terminal region of the Frizzled receptor 1 in detergent micelles Molecules 2013 18 7 8579 8590 10.3390/molecules18078579
Open DOI Search in Google Scholar Back to article
Zezula J Freissmuth M The A(2A)-adenosine receptor: a GPCR with unique features? Br J Pharmacol 2008 153 Suppl 1 S184 190 10.1038/sj.bjp.0707674
Open DOI Search in Google Scholar Back to article
Sensoy O Weinstein H A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1-PDZ-domain Biochim Biophys Acta 2015 1848 4 976 983 10.1016/j.bbamem.2014.12.002
Open DOI Search in Google Scholar Back to article
Tauriello DV Jordens I Kirchner K Slootstra JW Kruitwagen T Wnt/beta- catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled Proc Natl Acad Sci U S A 2012 109 14 E812 820 10.1073/pnas.1114802109
Open DOI Search in Google Scholar Back to article
Kolben T Perobner I Fernsebner K Lechner F Geissler C Dissecting the impact of Frizzled receptors in Wnt/beta-catenin signaling of human mesenchymal stem cells Biol Chem 2012 393 12 1433 1447 10.1515/hsz-2012-0186
Open DOI Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.5334/1750-2187-11-1 | Journal eISSN: 1750-2187

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Language: English

Page range: 1 - 1

Published on: Feb 5, 2016

Published by: Danny N. Dhanasekaran

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© 2016 Alexander C. Bertalovitz, Milly S. Pau, Shujuan Gao, Craig C. Malbon, Hsien-yu Wang, published by Danny N. Dhanasekaran
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 11 (2016): Issue 1