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Neuronal expression, cytosolic localization, and developmental regulation of the organic solute carrier partner 1 in the mouse brain
Authors:Hiratsuka Kazuyuki  Momose Atsushi  Takagi Norio  Sasaki Hiroyuki  Yin Shan-Ai  Fujita Mariko  Ohtomo Takayuki  Tanonaka Kouichi  Toyoda Hiroo  Suzuki Hisashi  Kurosawa Tohru  Yamada Junji
Institution:1. Toxicology Laboratory, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, Kanagawa, 230-0074, Japan
2. Department of Clinical Molecular Genetics, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan
3. Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan
5. Division of Molecular Cell Biology, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
4. Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo, 192-0392, Japan
6. Department of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan
Abstract:Organic solute carrier partner 1 (OSCP1) is a mammalian, transporter-related protein that is able to facilitate the uptake of structurally diverse organic compounds into the cell when expressed in Xenopus laevis oocytes. This protein has been implicated in testicular handling of organic solutes because its mRNA expression is almost exclusive in the testis. However, in this study, we demonstrated significant expression of OSCP1 protein in mouse brain, the level of which was rather higher than that in the testis, although the corresponding mRNA expression was one-tenth of the testicular level. Immunohistochemistry revealed that OSCP1 was broadly distributed throughout the brain, and various neuronal cells were immunostained, including pyramidal cells in the cerebral cortex and hippocampus. However, there was no evidence of OSCP1 expression in glia. In primary cultures of cerebral cortical neurons, double-labeling immunofluorescence localized OSCP1 to the cytosol throughout the cell body and neurites including peri-synaptic regions. This was consistent with the subcellular fractionation of brain homogenates, in which OSCP1 was mainly recovered after centrifugation both in the cytosolic fraction and the particulate fraction containing synaptosomes. Immunoelectron microscopy of brain sections also demonstrated OSCP1 in the cytosol near synapses. In addition, it was revealed that changes in the expression level of OSCP1 correlated with neuronal maturation during postnatal development of mouse brain. These results indicate that OSCP1 may have a role in the brain indirectly mediating substrate uptake into the neurons in adult animals.
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