Developmental and adult expression patterns of the G-protein-coupled receptor GPR88 in the rat: Establishment of a dual nuclear-cytoplasmic localization.
J. Comp. Neurol.. 2016-03-16; 524(14): 2776-2802
DOI: 10.1002/cne.23991
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Massart R(1)(2), Mignon V(1)(3), Stanic J(1), Munoz-Tello P(1), Becker JA(4), Kieffer BL(4), Darmon M(1), Sokoloff P(2), Diaz J(1)(3).
Author information:
(1)INSERM UMR894, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 75014, Paris, France.
(2)Neurology-Psychiatry Department, Pierre Fabre Research Institute, 81100, Castres, France.
(3)Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.
(4)Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, CNRS, INSERM, 67400, Illkirch-Graffenstaden, France.
GPR88 is a neuronal cerebral orphan G-protein-coupled receptor (GPCR) that has
been linked to various psychiatric disorders. However, no extensive description
of its localization has been provided so far. Here, we investigate the
spatiotemporal expression of the GPR88 in prenatal and postnatal rat tissues by
using in situ hybridization and immunohistochemistry. GPR88 protein was initially
detected at embryonic day 16 (E16) in the striatal primordium. From E16-E20 to
adulthood, the highest expression levels of both protein and mRNA were observed
in striatum, olfactory tubercle, nucleus accumbens, amygdala, and neocortex,
whereas in spinal cord, pons, and medulla GPR88 expression remains discrete. We
observed an intracellular redistribution of GPR88 during cortical lamination. In
the cortical plate of the developing cortex, GPR88 presents a classical GPCR
plasma membrane/cytoplasmic localization that shifts, on the day of birth, to
nuclei of neurons progressively settling in layers V to II. This intranuclear
localization remains throughout adulthood and was also detected in monkey and
human cortex as well as in the amygdala and hypothalamus of rats. Apart from the
central nervous system, GPR88 was transiently expressed at high levels in
peripheral tissues, including adrenal cortex (E16-E21) and cochlear ganglia
(E19-P3), and also at moderate levels in retina (E18-E19) and spleen (E21-P7).
The description of the GPR88 anatomical expression pattern may provide precious
functional insights into this novel receptor. Furthermore, the GRP88 nuclear
localization suggests nonclassical GPCR modes of action of the protein that could
be relevant for cortical development and psychiatric disorders. J. Comp. Neurol.
524:2776-2802, 2016. © 2016 Wiley Periodicals, Inc.