Neuropeptide GPCRs in neuroendocrinology: the case of activity-dependent neuroprotective protein (ADNP)

Abstract

VASOACTIVE INTESTINAL PEPTIDE (VIP): NEUROPROTECTION AND SYNAPSE FORMATION This review is a selected overview of the chosen subject. As, I have recently summarized my work on VIP (Gozes, 2008), I will describe here only selected topics focusing on the GPCR connection of the VIP-regulated protein, activity-dependent neuroprotective protein (ADNP) (Gozes, 2007). In the mid 1980s we were the first to clone the gene encoding the 28 amino acid neuropeptide, vasoactive intestinal peptide (VIP) (Bodner et al., 1985). This allowed us to follow up VIP gene expression in the brain showing developmental increases at the time of postnatal synapse formation and glial expansion (Gozes et al., 1987). Given the increased expression of VIP at the time of synapse formation and glial expansion, we hypothesized a developmental role for the peptide—associated with synaptogenesis and neuroprotection. Followup studies by the laboratory of Douglas Brenneman indeed showed that VIP provided neuroprotection through glial cells (Brenneman et al., 1987). We teamed up to show together with the group of Ronald McKay that VIP enhances synapse formation through glial cell activation (Blondel et al., 2000). Together with the late Frank Baldino, we showed extensive VIP mRNA expression in the brain, for example, in the suprachiasmatic nucleus (SCN) (Card et al., 1988), an area regulating diurnal rhythms. Our further studies utilizing our VIP hybrid antagonist showed that VIP function during development was required for maintenance of diurnal rhythmicity (Gozes et al., 1995). These findings were later confirmed by knocking out either VIP (Loh et al., 2011), or the VIP receptor VPAC2 (Harmar et al., 2002), which brings us to part of the subject of this review, GPCRs.