We recently cloned a full-length cDNA of the rat ATP-binding cassette transporter 2 (ABC2, or ABCA2) protein, a member of the ABC1 (or ABCA) subfamily (-ABC1/ABCA1 is a causal gene for Tangier disease) and found it to be strongly expressed in the rat brain. In this study, we identified ABC2 as a lysosomeassociated membrane protein that is being localized specifically in oligodendrocytes. The ABC2-immunolabeled cells were detected mainly in the white matter but were also scattered in gray matter throughout the whole brain. In addition, these cells were found to be colocalized with 2Ј,3Ј-cyclic nucleotide-3Ј-phosphodiesterase (CNPase) immunoreactivity when the marker antibody for oligodendrocytes was used. However, no such colocalization was observed with markers for other kinds of glial cells. Unlike the CNP antibody, which also intensely stains myelin sheaths in the white matter, ABC2 immunoreactivity was detected only in the cell bodies of oligodendrocytes. At the ultrastructural level, ABC2 immunoreactivity was detected mostly around lysosome and partly in Golgi apparatus by electron microscopy. This was confirmed by immunocolocalization of ABC2 and lysosomal markers in a neuroblastoma cell line. Immunoblotting analysis of ABC2 from the whole brain and the ABC2-transfected cell line revealed bands at ϳ260 kDa. The result of in situ hybridization with a riboprobe for ABC2 matched the results obtained from immunostaining. These findings strongly suggest that ABC2 is a specific marker for oligodendrocytes but not for myelinsheaths and that it is as a novel mammalian lysosome-associated membrane protein involved in myelinization or other kinds of metabolism in the CNS.
Recent studies have shown that a number of novel G-protein coupled receptor (GPCR) ligands localize in brain tissue and perform a range of physiological functions, some of which have been studied and clarified, and others about which less is known. Here, we wish to describe the distribution and localization of GPCR ligands identified thus far and to examine their involvement in neuronal networks, particularly those networks related to feeding regulation. The review analyzes published reports of morphological and physiological data looking mainly at the functional significance of feeding-regulation factors, such as those described by our research group and others, and neuronal interactions among these GPCR ligands in the hypothalamus. Cross-talk among several GPCR ligand-containing neuron types in the hypothalamus plays a role in determining feeding states. We introduce structural and functional characteristics of novel GPCR ligands and summarize the known interactions between several GPCR ligand-containing neuron types and leptin-targeting neurons in the hypothalamus. Finally, we present a new scheme summarizing neuronal networks with regard to feeding regulation in the hypothalamus. Research in this area will play an important role in clarifying neurologically-based causes for appetite dysfunction and establishing therapies for people suffering from such conditions.
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