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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Research article

A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway

Authors: Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas

Published in: Molecular Neurodegeneration | Issue 1/2017

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Abstract

Background

Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson’s disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson’s disease patients.

Methods

Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis’ early development.

Results

Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo.

Conclusions

Our study shows for the first time that LRRK2 activates the WNT/PCP signaling pathway through its interaction to multiple WNT/PCP components. We suggest that LRRK2 regulates the balance between WNT/β-catenin and WNT/PCP signaling, depending on the binding partners. Since this balance is crucial for homeostasis of midbrain dopaminergic neurons, we hypothesize that its alteration may contribute to the pathophysiology of Parkinson’s disease.
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Literature
1.
2.
Dachsel JC, Nishioka K, Vilarino-Guell C, Lincoln SJ, Soto-Ortolaza AI, Kachergus J, et al. Heterodimerization of Lrrk1-Lrrk2: implications for LRRK2-associated Parkinson disease. Mech Ageing Dev. 2010;131:210–4.PubMedPubMedCentralCrossRef
3.
4.
Wood-Kaczmar A, Gandhi S, Wood NW. Understanding the molecular causes of Parkinson's disease. Trends Mol Med. 2006;12:521–8.PubMedCrossRef
5.
Kumaran R, Cookson MR. Pathways to parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease. Hum Mol Genet. 2015;24:R32–44.PubMedPubMedCentralCrossRef
6.
Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F. A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol. 2002;51:296–301.PubMedCrossRef
7.
Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44:601–7.PubMedCrossRef
8.
Marin I, van Egmond WN, van Haastert PJ. The Roco protein family: a functional perspective. FASEB J. 2008;22:3103–10.PubMedCrossRef
9.
Angers S, Moon RT. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009;10:468–77.PubMedCrossRef
10.
Salinas PC. Wnt signaling in the vertebrate central nervous system: from axon guidance to synaptic function. Cold Spring Harb Perspect Biol. 2012;4(2):a008003.PubMedPubMedCentralCrossRef
11.
12.
Sato A, Yamamoto H, Sakane H, Koyama H, Kikuchi A. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29:41–54.PubMedCrossRef
13.
Andersson ER, Prakash N, Cajanek L, Minina E, Bryja V, Bryjova L, et al. Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo. PLoS One. 2008;3:e3517.PubMedPubMedCentralCrossRef
14.
Andersson ER, Salto C, Villaescusa JC, Cajanek L, Yang S, Bryjova L, et al. Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells. Proc Natl Acad Sci U S A. 2013;110:E602–10.PubMedPubMedCentralCrossRef
15.
Inestrosa NC, Arenas E. Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci. 2010;11:77–86.PubMedCrossRef
16.
Arenas E. Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease. J Mol Cell Biol. 2014;6:42–53.PubMedCrossRef
17.
Xiong H, Wang D, Chen L, Choo YS, Ma H, Tang C, et al. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J Clin Invest. 2009;119:650–60.PubMedPubMedCentralCrossRef
18.
Rawal N, Corti O, Sacchetti P, Ardilla-Osorio H, Sehat B, Brice A, et al. Parkin protects dopaminergic neurons from excessive Wnt/beta-catenin signaling. Biochem Biophys Res Commun. 2009;388:473–8.PubMedCrossRef
19.
Sancho RM, Law BM, Harvey K. Mutations in the LRRK2 roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways. Hum Mol Genet. 2009;18:3955–68.PubMedPubMedCentralCrossRef
20.
Berwick DC, Harvey K. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. Hum Mol Genet. 2012;21:4966–79.PubMedPubMedCentralCrossRef
21.
Giese AP, Ezan J, Wang L, Lasvaux L, Lembo F, Mazzocco C, et al. Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear. Development. 2012;139:3775–85.PubMedPubMedCentralCrossRef
22.
Perez VA, Ali Z, Alastalo TP, Ikeno F, Sawada H, Lai YJ, et al. BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways. J Cell Biol. 2011;192:171–88.PubMedCrossRef
23.
24.
Tao H, Suzuki M, Kiyonari H, Abe T, Sasaoka T, Ueno N. Mouse prickle1, the homolog of a PCP gene, is essential for epiblast apical-basal polarity. Proc Natl Acad Sci U S A. 2009;106:14426–31.PubMedPubMedCentralCrossRef
25.
Liu C, Lin C, Gao C, May-Simera H, Swaroop A, Li T. Null and hypomorph Prickle1 alleles in mice phenocopy human Robinow syndrome and disrupt signaling downstream of Wnt5a. Biology open. 2014;3:861–70.PubMedPubMedCentralCrossRef
26.
Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B, Copp AJ, et al. Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol. 2003;13:1129–33.PubMedCrossRef
27.
Morgan R, El-Kadi AM, Theokli C. Flamingo, a cadherin-type receptor involved in the drosophila planar polarity pathway, can block signaling via the canonical wnt pathway in Xenopus laevis. Int J Dev Biol. 2003;47:245–52.PubMed
28.
Son JH, Chun HS, Joh TH, Cho S, Conti B, Lee JW. Neuroprotection and neuronal differentiation studies using substantia nigra dopaminergic cells derived from transgenic mouse embryos. J Neurosci. 1999;19:10–20.PubMed
29.
Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science (New York, NY). 2014;343:84–7.CrossRef
30.
Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 2015;517:583–8.PubMedCrossRef
31.
Nieuwkoop P, Faber J: Normal table of Xenopus laevis (Daudin): a systematical and chronological survey of the development from the fertilized egg till the end of metamorphosis. 1994.
32.
Migheli R, Del Giudice MG, Spissu Y, Sanna G, Xiong Y, Dawson TM, et al. LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization. PLoS One. 2013;8:e77198.PubMedPubMedCentralCrossRef
33.
Stenman JM, Rajagopal J, Carroll TJ, Ishibashi M, McMahon J, McMahon AP. Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science (New York, NY). 2008;322:1247–50.CrossRef
34.
UniProt: a hub for protein information. Nucleic Acids Res 2015, 43:D204-D212.
35.
Hernandez-Valladares M, Aasebo E, Selheim F, Berven FS, Bruserud O. Selecting sample preparation workflows for mass spectrometry-based proteomic and Phosphoproteomic analysis of patient samples with acute myeloid leukemia. Proteomes. 2016;4
36.
Aasebo E, Mjaavatten O, Vaudel M, Farag Y, Selheim F, Berven F, et al. Freezing effects on the acute myeloid leukemia cell proteome and phosphoproteome revealed using optimal quantitative workflows. J Proteomics. 2016;145:214–25.PubMedCrossRef
37.
Terry DE, Umstot E, Desiderio DM. Optimized sample-processing time and peptide recovery for the mass spectrometric analysis of protein digests. J Am Soc Mass Spectrom. 2004;15:784–94.PubMedCrossRef
38.
Novak A, Hsu SC, Leung-Hagesteijn C, Radeva G, Papkoff J, Montesano R, et al. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways. Proc Natl Acad Sci U S A. 1998;95:4374–9.PubMedPubMedCentralCrossRef
39.
Rallis C, Pinchin SM, Ish-Horowicz D. Cell-autonomous integrin control of Wnt and notch signalling during somitogenesis. Development. 2010;137:3591–601.PubMedCrossRef
40.
41.
Habig K, Walter M, Poths S, Riess O, Bonin M. RNA interference of LRRK2-microarray expression analysis of a Parkinson's disease key player. Neurogenetics. 2008;9:83–94.PubMedCrossRef
42.
Angers S, Thorpe CJ, Biechele TL, Goldenberg SJ, Zheng N, MacCoss MJ, et al. The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. Nat Cell Biol. 2006;8:348–57.PubMedCrossRef
43.
Smalley MJ, Signoret N, Robertson D, Tilley A, Hann A, Ewan K, et al. Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta. J Cell Sci. 2005;118:5279–89.PubMedCrossRef
44.
Axelrod JD, Miller JR, Shulman JM, Moon RT, Perrimon N. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and wingless signaling pathways. Genes Dev. 1998;12:2610–22.PubMedPubMedCentralCrossRef
45.
Cliffe A, Hamada F, Bienz M. A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling. Current biology : CB. 2003;13:960–6.PubMedCrossRef
46.
Cajanek L, Ganji RS, Henriques-Oliveira C, Theofilopoulos S, Konik P, Bryja V, et al. Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. Mol Cell Biol. 2013;33:59–70.PubMedPubMedCentralCrossRef
47.
Gomez-Suaga P, Rivero-Rios P, Fdez E, Blanca Ramirez M, Ferrer I, Aiastui A, et al. Hum Mol Genet. 2014;23:6779–96.PubMedCrossRef
48.
MacLeod DA, Rhinn H, Kuwahara T, Zolin A, Di Paolo G, McCabe BD, et al. RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron. 2013;77:425–39.PubMedPubMedCentralCrossRef
49.
Dodson MW, Zhang T, Jiang C, Chen S, Guo M. Roles of the drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning. Hum Mol Genet. 2012;21:1350–63.PubMedCrossRef
50.
Shin N, Jeong H, Kwon J, Heo HY, Kwon JJ, Yun HJ, et al. LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res. 2008;314:2055–65.PubMedCrossRef
51.
Gonzalez-Sancho JM, Greer YE, Abrahams CL, Takigawa Y, Baljinnyam B, Lee KH, et al. Functional consequences of Wnt-induced dishevelled 2 phosphorylation in canonical and noncanonical Wnt signaling. J Biol Chem. 2013;288:9428–37.PubMedPubMedCentralCrossRef
52.
53.
Lee YN, Gao Y, Wang HY. Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, −2, and −3. Cell Signal. 2008;20:443–52.PubMedCrossRef
54.
Chan DW, Chan CY, Yam JW, Ching YP, Ng IO. Prickle-1 negatively regulates Wnt/beta-catenin pathway by promoting Dishevelled ubiquitination/degradation in liver cancer. Gastroenterology. 2006;131:1218–27.PubMedCrossRef
55.
Tree DR, Shulman JM, Rousset R, Scott MP, Gubb D, Axelrod JD. Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell. 2002;109:371–81.PubMedCrossRef
56.
Lin YY, Gubb D. Molecular dissection of drosophila prickle isoforms distinguishes their essential and overlapping roles in planar cell polarity. Dev Biol. 2009;325:386–99.PubMedCrossRef
57.
Sweede M, Ankem G, Chutvirasakul B, Azurmendi HF, Chbeir S, Watkins J, et al. Structural and membrane binding properties of the prickle PET domain. Biochemistry. 2008;47:13524–36.PubMedCrossRef
58.
59.
Skibinski G, Nakamura K, Cookson MR, Finkbeiner S. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J Neurosci. 2014;34:418–33.PubMedPubMedCentralCrossRef
60.
Reynolds A, Doggett EA, Riddle SM, Lebakken CS, Nichols RJ. LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status. Front Mol Neurosci. 2014;7:54.PubMedPubMedCentralCrossRef
61.
Volta M, Cataldi S, Beccano-Kelly D, Munsie L, Tatarnikov I, Chou P, et al. Chronic and acute LRRK2 silencing has no long-term behavioral effects, whereas wild-type and mutant LRRK2 overexpression induce motor and cognitive deficits and altered regulation of dopamine release. Parkinsonism Relat Disord. 2015;21:1156–63.PubMedCrossRef
62.
63.
Wallingford JB, Rowning BA, Vogeli KM, Rothbacher U, Fraser SE, Harland RM. Dishevelled controls cell polarity during Xenopus gastrulation. Nature. 2000;405:81–5.PubMedCrossRef
64.
65.
Carreira-Barbosa F, Kajita M, Morel V, Wada H, Okamoto H, Martinez Arias A, et al. Flamingo regulates epiboly and convergence/extension movements through cell cohesive and signalling functions during zebrafish gastrulation. Development. 2009;136:383–92.PubMedCrossRef
66.
67.
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. 1848;2015:976–83.
68.
Arango-Lievano M, Sensoy O, Borie A, Corbani M, Guillon G, Sokoloff P, et al. A GIPC1-Palmitate switch modulates dopamine Drd3 receptor trafficking and signaling. Mol Cell Biol. 2016;36:1019–31.PubMedPubMedCentralCrossRef
69.
Jeanneteau F, Diaz J, Sokoloff P, Griffon N. Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors. Mol Biol Cell. 2004;15:696–705.PubMedPubMedCentralCrossRef
70.
Jeanneteau F, Guillin O, Diaz J, Griffon N, Sokoloff P. GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling. Mol Biol Cell. 2004;15:4926–37.PubMedPubMedCentralCrossRef
71.
Kim J, Lee S, Ko S, Kim-Ha J. dGIPC is required for the locomotive activity and longevity in drosophila. Biochem Biophys Res Commun. 2010;402:565–70.PubMedCrossRef
72.
Choi I, Kim B, Byun JW, Baik SH, Huh YH, Kim JH, et al. LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase. Nat Commun. 2015;6:8255.PubMedPubMedCentralCrossRef
73.
Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, et al. Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature. 1996;379:91–6.PubMedCrossRef
74.
Filipenko NR, Attwell S, Roskelley C, Dedhar S. Integrin-linked kinase activity regulates Rac- and Cdc42-mediated actin cytoskeleton reorganization via alpha-PIX. Oncogene. 2005;24:5837–49.PubMedCrossRef
75.
Boulter E, Grall D, Cagnol S, Van Obberghen-Schilling E. Regulation of cell-matrix adhesion dynamics and Rac-1 by integrin linked kinase. FASEB J. 2006;20:1489–91.PubMedCrossRef
76.
James NG, Digman MA, Gratton E, Barylko B, Ding X, Albanesi JP, et al. Number and brightness analysis of LRRK2 oligomerization in live cells. Biophys J. 2012;102:L41–3.PubMedPubMedCentralCrossRef
77.
Sakaguchi-Nakashima A, Meir JY, Jin Y, Matsumoto K, Hisamoto N. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr Biol. 2007;17:592–8.PubMedCrossRef
78.
Arranz AM, Delbroek L, Van Kolen K, Guimaraes MR, Mandemakers W, Daneels G, et al. LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J Cell Sci. 2015;128:541–52.PubMedCrossRef
79.
Lee S, Imai Y, Gehrke S, Liu S, Lu B. The synaptic function of LRRK2. Biochem Soc Trans. 2012;40:1047–51.PubMedCrossRef
80.
Parisiadou L, Yu J, Sgobio C, Xie C, Liu G, Sun L, et al. LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity. Nat Neurosci. 2014;17:367–76.PubMedPubMedCentralCrossRef
81.
Piccoli G, Condliffe SB, Bauer M, Giesert F, Boldt K, De Astis S, et al. LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. J Neurosci. 2011;31:2225–37.PubMedCrossRef
82.
Borgs L, Peyre E, Alix P, Hanon K, Grobarczyk B, Godin JD, et al. Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects. Sci Rep. 2016;6:33377.PubMedPubMedCentralCrossRef
83.
Shimizu K, Sato M, Tabata T. The Wnt5/planar cell polarity pathway regulates axonal development of the drosophila mushroom body neuron. J Neurosci. 2011;31:4944–54.PubMedCrossRef
84.
Li X, Wang Y, Wang H, Liu T, Guo J, Yi W, et al. Epithelia-derived wingless regulates dendrite directional growth of drosophila ddaE neuron through the Fz-Fmi-Dsh-Rac1 pathway. Mol Brain. 2016;9:46.PubMedPubMedCentralCrossRef
85.
Steimel A, Wong L, Najarro EH, Ackley BD, Garriga G, Hutter H. The flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons in C. elegans. Development. 2010;137:3663–73.PubMedPubMedCentralCrossRef
86.
Mrkusich EM, Flanagan DJ, Whitington PM. The core planar cell polarity gene prickle interacts with flamingo to promote sensory axon advance in the drosophila embryo. Dev Biol. 2011;358:224–30.PubMedCrossRef
87.
Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, et al. Mutations in prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet. 2011;88:138–49.PubMedPubMedCentralCrossRef
88.
Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, et al. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet. 2008;83:572–81.PubMedPubMedCentralCrossRef
89.
Fox MH, Bassuk AG. PRICKLE1-related progressive Myoclonus epilepsy with ataxia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, Bird TD, Fong CT, Mefford HC, RJH S, Stephens K, editors. GeneReviews(R). Seattle: University of Washington, Seattle University of Washington, Seattle. All rights reserved; 1993.
90.
Paemka L, Mahajan VB, Skeie JM, Sowers LP, Ehaideb SN, Gonzalez-Alegre P, et al. PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. PLoS One. 2013;8:e80737.PubMedPubMedCentralCrossRef
91.
92.
Nagaoka T, Ohashi R, Inutsuka A, Sakai S, Fujisawa N, Yokoyama M, et al. The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin. Cell Rep. 2014;6:916–27.PubMedCrossRef
93.
Chen J, Park CS, Tang SJ. Activity-dependent synaptic Wnt release regulates hippocampal long term potentiation. J Biol Chem. 2006;281:11910–6.PubMedCrossRef
94.
Farias GG, Alfaro IE, Cerpa W, Grabowski CP, Godoy JA, Bonansco C, et al. Wnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons. J Biol Chem. 2009;284:15857–66.PubMedPubMedCentralCrossRef
95.
Nixon-Abell J, Berwick DC, Granno S, Spain VA, Blackstone C, Harvey K. Protective LRRK2 R1398H variant enhances GTPase and Wnt signaling activity. Front Mol Neurosci. 2016;9:18.PubMedPubMedCentralCrossRef
96.
Chan D, Citro A, Cordy JM, Shen GC, Wolozin B. Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2). J Biol Chem. 2011;286:16140–9.PubMedPubMedCentralCrossRef
97.
Lindqvist M, Horn Z, Bryja V, Schulte G, Papachristou P, Ajima R, et al. Vang-like protein 2 and Rac1 interact to regulate adherens junctions. J Cell Sci. 2010;123:472–83.PubMedPubMedCentralCrossRef
98.
Berwick DC, Javaheri B, Wetzel A, Hopkinson M, Nixon-Abell J, Granno S, et al. Pathogenic LRRK2 variants are gain-of-function mutations that enhance LRRK2-mediated repression of beta-catenin signaling. Mol Neurodegener. 2017;12:9.PubMedPubMedCentralCrossRef
99.
Gao B, Song H, Bishop K, Elliot G, Garrett L, English MA, et al. Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. Dev Cell. 2011;20:163–76.PubMedPubMedCentralCrossRef
100.
Kuss P, Kraft K, Stumm J, Ibrahim D, Vallecillo-Garcia P, Mundlos S, et al. Regulation of cell polarity in the cartilage growth plate and perichondrium of metacarpal elements by HOXD13 and WNT5A. Dev Biol. 2014;385:83–93.PubMedCrossRef
101.
Lu C, Wan Y, Cao J, Zhu X, Yu J, Zhou R, et al. Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification. Bone. 2013;53:566–74.PubMedCrossRef
102.
103.
Gandhi PN, Wang X, Zhu X, Chen SG, Wilson-Delfosse AL. The roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules. J Neurosci Res. 2008;86:1711–20.PubMedPubMedCentralCrossRef
104.
Liu GH, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, et al. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature. 2012;491:603–7.PubMedPubMedCentralCrossRef
105.
Wang L, Xie C, Greggio E, Parisiadou L, Shim H, Sun L, et al. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J Neurosci. 2008;28:3384–91.PubMedPubMedCentralCrossRef
106.
107.
Tan C, Deardorff MA, Saint-Jeannet JP, Yang J, Arzoumanian A, Klein PS. Kermit, a frizzled interacting protein, regulates frizzled 3 signaling in neural crest development. Development. 2001;128:3665–74.PubMed
108.
109.
Djiane A, Mlodzik M. The drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development. PLoS One. 2010;5:e11228.PubMedPubMedCentralCrossRef
110.
Grunewald TG, Pasedag SM, Butt E. Cell adhesion and transcriptional activity - defining the role of the novel Protooncogene LPP. Transl Oncol. 2009;2:107–16.PubMedPubMedCentralCrossRef
111.
Ngan E, Northey JJ, Brown CM, Ursini-Siegel J, Siegel PM. A complex containing LPP and alpha-actinin mediates TGFbeta-induced migration and invasion of ErbB2-expressing breast cancer cells. J Cell Sci. 2013;126:1981–91.PubMedPubMedCentralCrossRef
112.
Petit MM, Meulemans SM, Alen P, Ayoubi TA, Jansen E, Van de Ven WJ. The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus. BMC Cell Biol. 2005;6:1.PubMedPubMedCentralCrossRef
113.
Vervenne HB, Crombez KR, Lambaerts K, Carvalho L, Koppen M, Heisenberg CP, et al. Lpp is involved in Wnt/PCP signaling and acts together with Scrib to mediate convergence and extension movements during zebrafish gastrulation. Dev Biol. 2008;320:267–77.PubMedCrossRef
114.
Wu C, Keightley SY, Leung-Hagesteijn C, Radeva G, Coppolino M, Goicoechea S, et al. Integrin-linked protein kinase regulates fibronectin matrix assembly, E-cadherin expression, and tumorigenicity. J Biol Chem. 1998;273:528–36.PubMedCrossRef
115.
Wu X, Wang J, Jiang H, Hu Q, Chen J, Zhang J, et al. Wnt3a activates beta1-integrin and regulates migration and adhesion of vascular smooth muscle cells. Mol Med Rep. 2014;9:1159–64.PubMed
116.
Lanni C, Necchi D, Pinto A, Buoso E, Buizza L, Memo M, et al. Zyxin is a novel target for beta-amyloid peptide: characterization of its role in Alzheimer's pathogenesis. J Neurochem. 2013;125:790–9.PubMedCrossRef
117.
Martynova NY, Ermolina LV, Ermakova GV, Eroshkin FM, Gyoeva FK, Baturina NS, et al. The cytoskeletal protein Zyxin inhibits Shh signaling during the CNS patterning in Xenopus laevis through interaction with the transcription factor Gli1. Dev Biol. 2013;380:37–48.PubMedCrossRef
118.
Luo S, Schaefer AM, Dour S, Nonet ML. The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance in Caenorhabditis elegans. Development. 2014;141:3922–33.PubMedPubMedCentralCrossRef
119.
van Wijk NV, Witte F, Feike AC, Schambony A, Birchmeier W, Mundlos S, et al. The LIM domain protein Wtip interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signalling. Biochem Biophys Res Commun. 2009;390:211–6.PubMedCrossRef
120.
Hansen SD, Mullins RD. Lamellipodin promotes actin assembly by clustering Ena/VASP proteins and tethering them to actin filaments. Elife. 2015;4
121.
Krause M, Leslie JD, Stewart M, Lafuente EM, Valderrama F, Jagannathan R, et al. Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Dev Cell. 2004;7:571–83.PubMedCrossRef
122.
Vehlow A, Soong D, Vizcay-Barrena G, Bodo C, Law AL, Perera U, et al. Endophilin, Lamellipodin, and Mena cooperate to regulate F-actin-dependent EGF-receptor endocytosis. EMBO J. 2013;32:2722–34.PubMedPubMedCentralCrossRef
123.
Tasaka G, Negishi M, Oinuma I. Semaphorin 4D/Plexin-B1-mediated M-Ras GAP activity regulates actin-based dendrite remodeling through Lamellipodin. J Neurosci. 2012;32:8293–305.PubMedCrossRef
Metadata
Title
A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway
Authors
Alena Salašová
Chika Yokota
David Potěšil
Zbyněk Zdráhal
Vítězslav Bryja
Ernest Arenas
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0193-9

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