Interactions of Visinin-like Proteins with Phospho-inositides

Karl-Heinz Braunewell; Blessy Paul; Wassim Altarche-Xifro; Cornelia Noack; Kristian Lange; Andreas Hofmann

doi:10.1071/CH09355

RESEARCH FRONT

Interactions of Visinin-like Proteins with Phospho-inositides

Karl-Heinz Braunewell ^A ^B , Blessy Paul ^C , Wassim Altarche-Xifro ^A , Cornelia Noack ^A , Kristian Lange ^A and Andreas Hofmann ^C ^D

+ Author Affiliations

- Author Affiliations

^A Signal Transduction Research Group, Neuroscience Research Center/Institute for Neurophysiology, Charité Berlin, Germany.

^B Molecular & Cellular Neuroscience Laboratory, Biochemistry & Molecular Biology Department, Southern Research Institute, Birmingham, AL 35205, USA.

^C Structural Chemistry Program, Eskitis Institute for Cell & Molecular Therapies, Griffith University, Brisbane, Qld 4111, Australia.

^D Corresponding author. Email: a.hofmann@griffith.edu.au

Australian Journal of Chemistry 63(3) 350-356 https://doi.org/10.1071/CH09355
Submitted: 21 June 2009 Accepted: 30 July 2009 Published: 26 March 2010

Abstract

The subcellular membrane localization of neuronal calcium sensor (NCS) proteins in living cells, such as Visinin-like Proteins-1 (VILIP-1) and VILIP-3, differs substantially. We have followed the hypothesis that the differential localization may be due to the specific binding capabilities of individual VILIPs for phosphatidylinositol phosphates (PIPs). Several highly conserved lysine residues in the N-terminal region could provide favourable electrostatic interactions. Molecular modelling results support a binding site for phospho-inositides in the N-terminal area of VILIP-1, and the involvement of the conserved N-terminal lysine residues in binding the phospho-inositol head group. Experimentally, the binding of VILIP-1 to inositol derivatives was tested by a PIP strip assay, which showed the requirement of phosphorylation of the inositol group for the interaction of the protein with PIPs. Monolayer adsorption measurements showed a preference of VILIP-1 binding to PI(4,5)P₂ over PI(3,4,5)P₃. The co-localization of VILIP-1 with PI(4,5)P₂ at the cell surface membrane in hippocampal neurons further supports the idea of direct interactions of VILIP-1 with PIPs in living cells.

Acknowledgements

We gratefully acknowledge funding by Fundacao Bial, the European League Against Rheumatism (EULAR), and the Rebecca L Cooper Foundation to A.H., and funding by Deutsche Forschungsgemeinschaft to K.-H.B. (DFG Br-1579/8–1, Priority Program of the German Research Foundation, SPP1226 ‘Nicotine’, GRK 1123). Blessy Paul is recipient of a Griffith University International Research Scholarship. Wassim Altarche-Xifro is a qualifying student in the GRK program 1123 of the DFG.

References

Interactions of Visinin-like Proteins with Phospho-inositides

Abstract

Acknowledgements

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