Dr Clotilde Lévecque

Research

I first joined the Monaco group to work on the functional characterization of the VPS13 protein family (VPS13A/Chorein, VPS13B, C and D). Recently, some mutations in the VPS13A and in VPS13B (or COH1) genes have been identified in Chorea-acanthocytosis (ChAc) patients and Cohen syndrome respectively. The genes encoding these proteins have been characterized but, to date, we have no information on the function of these human proteins.

In June 2006, I got involved in the dyslexia project. We have previously described a risk haplotype associated with dyslexia and shown that this haplotype is associated with a reduction of KIAA0319 gene expression. Interference with rat Kiaa0319 expression in utero disrupts neuronal migration in the developing cerebral cortex. However, the precise function of this protein and its involvement in neuronal migration are still unclear. In order to gain more information on KIAA0319 function, I performed several yeast two hybrid screens, using different fragments of KIAA0319 as baits, which led to the identification of several potential binding partners. Further analysis on the first candidate identified, AP-2, have shown that, after KIAA0319 reaches the plasma membrane, it is internalized back into the cell via a clathrin mediated pathway. I am actually following up the results of the yeast two hybrid screens, to confirm the interaction detected using others methods and to characterized the biological effects of these interactions.

I am a STEM Ambassador (www.stemnet.org.uk/content/ambassadors) and occasionally help out with public engagement activities such as workshops here at the Wellcome Trust Centre for Human Genetics or in schools or for events such as Science in the kitchen/Oxfordshire Science festival.

Publications

Velayos-Baeza A, Levecque C, Kobayashi K, Holloway ZG, Monaco AP. (2010) The dyslexia-associated KIAA0319 protein undergoes proteolytic processing with {gamma}-secretase-independent intramembrane cleavage. J Biol Chem. Oct 13. PMID: 20943657
Levecque C, Velayos-Baeza A, Holloway ZG, Monaco AP.The dyslexia-associated protein KIAA0319 interacts with Adaptor Protein 2 and follows the classical clathrin-mediated endocytosis pathway. Am J Physiol Cell Physiol. 2009 May 6. PMID: 19419997
Chartier-Harlin M-C, KachergusJ, Roumier C, Mouroux V, Douay X, LincolnS, LévecqueC, et al; α-synuclein locus duplication causes familial Parkinson's disease. Lancet. 2004 Sep 25-Oct 1;364(9440):1167-9. PMID: 15451224
Lévecque C, Destée A, Mouroux V, Amouyel P, Chartier-Harlin M-C; Assessment of Nurr1 nucleotidic variations in familial Parkinson's disease. Neurosci lett. 2004 Aug 12;366(2):135-8. PMID: 15276233
Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin M‑C, Gasser T, Krüger R, Hattori N, Mellick GD, Quattrone A, Satoh J-I, Toda T, Wang J, Ioannidis JPA, Rocca WA and the UCHL1 Global Genetics Consortium*. UCHL1 is a Parkinson's Disease Susceptibility Gene. Ann Neurol. 2004 Apr;55(4):512-21. *The UCHL1 Global Genetics Consortium includes 30 investigators, who are all authors of this manuscript. PMID: 15048890
Elbaz A, Lévecque C, Clavel J, Vidal J‑S, Richard F, et al; CYP2D6 polymorphism, exposure to pesticides, and Parkinson's disease. Annals of Neurology. 2004 Mar;55(3):430-4. PMID: 14991823
Lévecque C, Elbaz A, Clavel J, Vidal J-S, Amouyel P, et al; Association of polymorphisms in the Tau and Saitohin genes with Parkinson's disease. JNeurol Neurosurg Psychiatry. 2004 Mar; 75(3):478-80. PMID: 14966169
Lévecque C*, Elbaz A*, Clavel J, Richard F, Vidal J-S, et al; Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study. Hum Mol Genet. 2003, vol. 12 (1): 79-86. * equally contributed to this work. PMID: 12490535
Elbaz A, Lévecque C, Clavel J, Vidal J-S, Richard F et al; The S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relation. Mov Disord. 2003; vol.18 (2): 130-137. PMID: 12539205
Lévecque C, Destée A, Mouroux V, Becquet E, Defebvre L, et al; No genetic association of the Ubiquitin Carboxy-terminal Hydrolase-L1 gene S18Y polymorphism with familial Parkinson's disease. J Neural Transm. 2001; 108: 979-984. PMID: 11716150
Farrer M, Destée A, Lévecque C, Singleton A, Engelender S et al; Genetic analysis of synphilin-1 in familial Parkinson's disease. Neurobiolo Dis. 2001 Apr; 8 (2): 317-23. PMID: 11300726

BOOK CHAPTER

Velayos-Baeza A., Lévecque C., Dobson-Stone C., Monaco AP. The function of chorein. Neuroacanthocytosis syndromes II. 87-105. 2008.