title: Anatomical and ultrastructural study of PRAF2 expression in the mouse central nervous system.
abstract: Prenylated Rab acceptor family, member 2 (PRAF2) is a four transmembrane domain protein of 19 kDa that is highly expressed in particular areas of mammalian brains. PRAF2 is mostly found in the endoplasmic reticulum (ER) of neurons where it plays the role of gatekeeper for the GB1 subunit of the GABABreceptor, preventing its progression in the biosynthetic pathway in the absence of hetero-dimerization with the GB2 subunit. However, PRAF2 can interact with several receptors and immunofluorescence studies indicate that PRAF2 distribution is larger than the ER, suggesting additional biological functions. Here, we conducted an immuno-cytochemical study of PRAF2 distribution in mouse central nervous system (CNS) at anatomical, cellular and ultra-structural levels. PRAF2 appears widely expressed in various regions of mature CNS, such as the olfactory bulbs, cerebral cortex, amygdala, hippocampus, ventral tegmental area and spinal cord. Consistent with its regulatory role of GABABreceptors, PRAF2 was particularly abundant in brain regions known to express GB1 subunits. However, other brain areas where GB1 is expressed, such as basal ganglia, thalamus and hypothalamus, contain little or no PRAF2. In these areas, GB1 subunits might reach the cell surface of neurons independently of GB2 to exert biological functions distinct from those of GABABreceptors, or be regulated by other gatekeepers. Electron microscopy studies confirmed the localization of PRAF2 in the ER, but identified previously unappreciated localizations, in mitochondria, primary cilia and sub-synaptic region. These data indicate additional modes of GABABregulation in specific brain areas and new biological functions of PRAF2.
authors.affiliation: Institut du Fer à Moulin, INSERM UMR-S839, Université Pierre et Marie Curie, 75005, Paris, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cifuentes-Diaz
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, 27 rue du Faubourg St-Jacques, 75014, Paris, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marullo
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, 27 rue du Faubourg St-Jacques, 75014, Paris, France. stephane.doly@inserm.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Doly
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D013116:Spinal Cord / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C498435:Rabac1 protein, mouse; D033921:Vesicular Transport Proteins
keywords: CNS; Cilium; GABA(B) receptor; JM4; PRAF2; Synapse