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 GABAB receptor, 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 GABAB receptors, 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 GABAB receptors, 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 GABAB regulation in specific brain areas and new biological functions of PRAF2.
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Abbreviations
- 10cb:
-
Tenth cerebellar lobule
- 10N:
-
Dorsal motor nucleus of vagus
- 12N:
-
Hypoglossal nucleus
- 7N:
-
Facial nucleus
- aca:
-
Anterior commissure anterior part
- AcbC:
-
Accumbens nucleus core
- AcbSh:
-
Accumbens nucleus shell
- aci:
-
Anterior commissure intrabulbar part
- AD:
-
Anterodorsal thalamic nucleus
- Amb:
-
Ambiguus nucleus
- AOV:
-
Anterior olfactory nucleus ventral part
- AP:
-
Area postrema
- BM:
-
Basomedial amygdaloid nucleus
- BST:
-
Bed nucleus of the stria terminalis
- CNS:
-
Central nervous system
- Cp:
-
Corpus callosum
- CPu:
-
Caudate putamen
- cu:
-
Cuneate fasciculus
- Cu:
-
Cuneate nucleus
- DAB:
-
Diaminobenzidine
- DC:
-
Dorsal cochlear nucleus
- Den:
-
Dorsal endopiriform nucleus
- DG:
-
Dentate gyrus
- DH:
-
Dorsal horn
- DR:
-
Dorsal raphe nucleus
- Ecu:
-
External cuneate nucleus
- EPL:
-
External plexiform layer
- ER:
-
Endoplasmic reticulum
- GABA:
-
Gamma-amino butyric acid
- GCL:
-
Granule cell layer
- Gi:
-
Gigantocellular reticular nucleus
- Gl:
-
Glomerular layer of the olfactory bulb
- GPCRs:
-
G protein coupled receptors
- Gr:
-
Gracile nucleus
- GR:
-
Granular cells layer
- H:
-
Hilus
- Io:
-
Inferior olive
- IOC:
-
Inferior olive subnucleus C
- IP:
-
Interpeduncular nucleus
- LGP:
-
Lateral globus pallidus
- LH:
-
Lateral hypothalamic area
- LHb:
-
Lateral habenular nucleus
- LM:
-
Lateral mammillary nucleus
- LRt:
-
Lateral reticular nucleus
- M2:
-
Secondary motor cortex
- MdV:
-
Medullary reticular nucleus ventral part
- Med:
-
Medial fastigial cerebellar nucleus
- MePD:
-
Medial amygdaloid nucleus posterodorsal part
- MG:
-
Medial geniculate nucleus
- MHb:
-
Medial habenular nucleus
- Mi:
-
Mitral cell layer of the olfactory bulb
- ML:
-
Molecular layer
- MM:
-
Medial mammillary nucleus
- MnR:
-
Median raphe nucleus
- MO:
-
Medial orbital cortex
- MVB:
-
Multivesicular bodies
- MVePC:
-
Medial vestibular nucleus parvicellular part
- Or:
-
Strata oriens
- PAG:
-
Periaqueductal gray
- Par:
-
Parietal cortex
- PFl:
-
Paraflocculus
- Pir:
-
Piriform cortex
- PMCo:
-
Posteromedial cortical amygdaloid nucleus
- Pn:
-
Pontine nuclei
- PRAF2:
-
Prenylated Rab acceptor family, member 2
- Prl:
-
Prelimbic cortex
- Pur:
-
Purkinje cells layer
- PVA:
-
Paraventricular thalamic nucleus
- Pyr:
-
Pyramidal cells
- Rad:
-
Stratum radiatum
- RER:
-
Rough endoplasmic reticulum
- Rt:
-
Reticular thalamic nucleus
- sm:
-
Stria medullaris thalamus
- SNC:
-
Substancia nigra compacta
- SNR:
-
Substantia nigra pars reticulate
- Sol:
-
Nucleus of the solitary tract
- Sp5:
-
Spinal trigeminal nucleus
- VCP:
-
Ventral cochlear nucleus posterior part
- VH:
-
Ventral horn
- VL:
-
Ventrolateral nucleus
- VMH:
-
Ventromedial hypothalamic nucleus
- VPM:
-
Ventral posteromedial thalamic nucleus
- VTA:
-
Ventral tegmental area
- Zo:
-
Zonal layer of superior colliculus
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Acknowledgments
This work was supported by grants from the Ligue Contre le Cancer, comité de l’Oise to SD; from the PIC (projets inter-équipes) to SD; from the French Agency for AIDS Research (ANRS-09) and the Fondation pour la Recherche Médicale (Equipe FRM-2012) to SM; SM team is member of the ‘Who-am-I’ research consortium.
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Cifuentes-Diaz, C., Marullo, S. & Doly, S. Anatomical and ultrastructural study of PRAF2 expression in the mouse central nervous system. Brain Struct Funct 221, 4169–4185 (2016). https://doi.org/10.1007/s00429-015-1159-8
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DOI: https://doi.org/10.1007/s00429-015-1159-8