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Karl-Heinz Braunewell" Neuronal calcium sensors as candidate plasticity genes"

Abstract :

A variety of calcium-sensing proteins have been identified in the nervous system in addition to the ubiquitous calcium sensor calmodulin, reflecting the importance of calcium and its regulative function in nerve cells.
Neuronal calcium sensors (NCS) comprise a family of 15 closely related EF-hand calcium-binding proteins which have multiple key roles in controlling neuronal function in health and disease. Recently, NCS proteins have become a focus of interest as plasticity candidate genes. The NCS protein VILIP-1 (visinin-like protein 1) is expressed at high levels in the rat hippocampus and shows increased expression following electrical and chemical induction of LTP in the hippocampal formation. In cultured hippocampal neurons VILIP-1 shows mGluR-dependent expression and stimulus-dependent and reversible translocation to Golgi and cell surface membranes. The calcium- and myristoylation dependent membrane association, the calcium-myristoyl switch of VILIP-1, might provide a fast signalling mechanism to influence membrane-associated signalling effectors.

In line with this notion, we have observed effects of VILIP-1 on membrane-localized signalling systems including the nicotinic acetylcholine receptor α4ß2 and the receptor guanylyl cyclase GC-B. Both receptors are highly expressed in hippocampal neurons and calcium-dependently co-localize with VILIP-1. Overexpression of VILIP-1 increases the agonist sensitivity of the nAChR in the oocyte expression system and VILIP-1 activates cGMP accumulation following stimulation of GC-B with the agonist CNP (C-type natriuretic peptide) in hippocampal neurons. In order to investigate the molecular mechanisms underlying receptor modulation by VILIP-1, we have examined the influence on cell surface expression and receptor trafficking. We postulate that the plasticity candidate gene VILIP-1 is a general modulator of receptor trafficking and, thus, might be a modulator of hippocampal synaptic plasticity.


Selected publications

Ren XQ, Cheng SB, Treuil MW, Mukherjee J, Rao J, Braunewell KH, Lindstrom JM, Anand R.
Structural determinants of alpha4beta2 nicotinic acetylcholine receptor trafficking.
J Neurosci. 2005 Jul 13;25(28):6676-86.

Braunewell KH.
The darker side of Ca2+ signaling by neuronal Ca2+-sensor proteins: from Alzheimer's disease to cancer.
Trends Pharmacol Sci. 2005 Jul;26(7):345-51.

Christophe Mulle