interferenceTM

Three academic groups representing cell biology, molecular biophysics and computational chemistry propose to investigate neuropilins signalling platforms and their potential as drug targets. Neuropilins are cell surface receptors that play a central role in the development and maintenance of the nervous and vascular systems. Signal mediation relies on their interactions with multiple other membrane proteins, interactions that are at the centre of this request. The assembly of these signalling complexes is poorly understood to date, although neuropilins play a role in diseases of the nervous system, as well as cancer, and are considered as promising drug targets. The Strasbourg (D. Bagnard) and Marseille (J. Sturgis, P. Hubert) groups have recently demonstrated that a peptide corresponding to the native transmembrane (TM) sequence of neuropilin 1 inhibits selectively neuropilin signalling both in vitro and in vivo (Roth et al. Mol. Biol. Cell 2008; Nasarre et al. Oncogene 2010). This short peptide is an extremely potent antagonist in all assays performed so far, it is thus a very promising venture to explore in greater details the molecular mechanisms of signaling platforms assembly through TM interactions by biochemical, biophysical anf computer modeling techniques; as well as determining the pharmacological properties of selected peptides or peptidomimetic stuctures. Focusing on the role of the TM domains is a novel research avenue that will certainly be useful in many areas of membrane biology and biotechnology while possessing an extraordinary therapeutic potential in the long run.