Visinin-like proteins (VSNLs): interaction partners and emerging functions in signal transduction of a subfamily of neuronal Ca²⁺-sensor proteins

• Published in: Cell and tissue research 2009-02, Vol.335 (2), p.301-316
• Main Authors: Braunewell, Karl-Heinz, Szanto, Andres J. Klein
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biomedical and Life Sciences; Biomedical research; Biomedicine; Calcium - metabolism; Calcium-myristoyl switch; cAMP/cGMP signaling; Cellular biology; Central Nervous System - metabolism; Comparative studies; endocytosis; exocytosis; Gene Expression; Human Genetics; Humans; MAPK pathways; Molecular Medicine; Molecular Sequence Data; Neurocalcin - metabolism; Neurodegeneration; Neuronal calcium sensors; Neuronal Calcium-Sensor Proteins - metabolism; Protein Transport; Proteins; Proteomics; Review; Signal Transduction
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-008-0716-3

The visinin-like protein (VSNL) subfamily, including VILIP-1 (the founder protein), VILIP-2, VILIP-3, hippocalcin, and neurocalcin δ, constitute a highly homologous subfamily of neuronal calcium sensor (NCS) proteins. Comparative studies have shown that VSNLs are expressed predominantly in the brain with restricted expression patterns in various subsets of neurons but are also found in peripheral organs. In addition, the proteins display differences in their calcium affinities, in their membrane-binding kinetics, and in the intracellular targets to which they associate after calcium binding. Even though the proteins use a similar calcium-myristoyl switch mechanism to translocate to cellular membranes, they show calcium-dependent localization to various subcellular compartments when expressed in the same neuron. These distinct calcium-myristoyl switch properties might be explained by specificity for defined phospholipids and membrane-bound targets; this enables VSNLs to modulate various cellular signal transduction pathways, including cyclic nucleotide and MAPK signaling. An emerging theme is the direct or indirect effect of VSNLs on gene expression and their interaction with components of membrane trafficking complexes, with a possible role in membrane trafficking of different receptors and ion channels, such as glutamate receptors of the kainate and AMPA subtype, nicotinic acetylcholine receptors, and Ca²⁺-channels. One hypothesis is that the highly homologous VSNLs have evolved to fulfil specialized functions in membrane trafficking and thereby affect neuronal signaling and differentiation in defined subsets of neurons. VSNLs are involved in differentiation processes showing a tumor-invasion-suppressor function in peripheral organs. Finally, VSNLs play neuroprotective and neurotoxic roles and have been implicated in neurodegenerative diseases.