MODULATING AQUAPORIN FUNCTION WITH PEPTIDE APTAMERS

The objective of this proposal is to facilitate the exchange between the CNRS/ENS Lyon Team and the University of Oslo Team to investigate the effect of specific peptide aptamers on aquaporin (AQP) function while investigating the expression and fate of A QP-interacting proteins. A fortuitous observation by the Lyon team has uncovered an interesting molecule called a peptide aptamer that has significant similarity (90%) to a portion of one of the AQP. This peptide aptamer activates a protein phosphatase ca lled Calcineurin A (CnA), of major physiological importance in the immune system and in other critical cellular processes of medical import. The peptide aptamer has shown beneficial effects in a mouse model for acute muscle atrophy. AQP modulate water per meability of biological membranes, or water plus glycerol. The Oslo Team, one of the world leaders in the field, have contributed to the discovery of their involvement in important physiological processes such as maintenance of body water homeostasis, but are also involved in pathological conditions such as cataract and brain edema. This collaboration aims to ascertain if there is a relation between the activity of the peptide aptamer towards CnA and aquaporin activity, expression or fate in selected mode ls mastered by the Oslo Team. Further, the Lyon Team aims to use its know-how for the study of expression and fate of membrane proteins in lipid rafts to address questions of import to the Oslo Team. Notably, the association of aquaporins with other membr ane proteins of import to neuronal signaling. The Lyon Team Leader was invited as Asgard Scholar to Norway in 2009, initiating the present request. After giving seminars and interaction with several centers of excellence, the Laboratory of Molecular Neuro science was identified as having technologies and know-how complementary to the Lyon Team. A subsequent visit from the Oslo Team Leader to Lyon confirmed the interest, setting the stage for this request.