Fourth International Symposium on Neuroacanthocytosis

Abstracts from the Fourth International Symposium on Neuroacanthocytosis

July 1-2, 2008
London and Oxford

Chairs: Prof. Kailash Bhatia, MD, FRCP, Institute of Neurology, University College London; Prof. Anthony P. Monaco, MD, PhD, Wellcome Trust Centre for Human Genetics, University of Oxford

Organizers: Antonio Velayos-Baeza, PhD; Susanne Schneider, MD; Glenn Irvine

4-3 Chorein and other human VPS13 proteins
C. Lévecque, A. Velayos-Baeza, and A. P. Monaco
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

The VPS13 protein family includes four members: VPS13A, VPS13B, VPS13C and VPS13D. Chorein, encoded by the VPS13A gene, is altered in Chorea-Acanthocytosis (ChAc) and the VPS13B gene, also known as COH1, is mutated in Cohen syndrome. Sequence analysis of these four large proteins did not reveal any domain that could provide information about the possible function of these proteins. However, their yeast homologue, Vps13p has been shown to be involved in the trafficking of several proteins between the trans-Golgi network and the prevacuolar compartment. We present here a review of the data obtained on VPS13 proteins. The investigation of their subcellular localisation shows that they are soluble cytoplasmic proteins that interact with membranes. A characteristic vesicular-like pattern is easily detected in cells expressing chorein; similar structures can also be detected for VPS13B, C or D but at a much lower occurrence. The characteristic vesicular-like pattern of chorein is altered in several of the mutated chorein proteins suggesting that this pattern reflects a functionally important localisation. We have used an immunoprecipitation approach to test whether the VPS13 proteins form homo- or heterodimers (or multimers). We also investigated the potential interaction between VPS13 proteins and candidates partners such as proprotein convertases or MADD.