Fig. 3. The VSNL-subfamily of NCS proteins may serve as Ca²⁺-dependent modulators of membrane receptor trafficking.

Following neurotransmitter activation and neuronal activity VSNLs Ca²⁺-dependently translocate to intracellular and cell surface membranes. VILIP-1 is a modulator of membrane-localized natriuretic peptide receptor (GCs) and nicotinic acetylcholine receptor (nAChRs) function and trafficking (Lin et al., 2002; Brackmann et al., 2005; Gierke et al., 2008). Similar to VILIP-1, neurocalcin δ and hippocalcin have been identified as modulators of guanylyl cyclase (olfactory and retinal guanylyl cyclase receptors) (Mammen et al., 2004). Moreover, VILIP-1 and neurocalcinδ have been implicated in modulating the trafficking of glutamate receptors of the kainate subtype (Coussen et al., 2006; Coussen and Mulle, 2006). Hippocalcin acts as a Ca²⁺ sensor for AMPA receptor endocytotic trafficking (Palmer et al., 2005). Thus, VSNLs might influence membrane trafficking of receptors at different check points, such as endo- or exocytosis or receptor recycling.