Wang M, Suzuki T, Kitada T, Asakawa S, Minoshima S, Shimizu N, Tanaka K, Mizuno Y, Hattori N
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
J Neurochem. 2001 Jun;77(6):1561-8. doi: 10.1046/j.1471-4159.2001.00372.x.
Parkin is a product of the Park2 gene the mutation of which causes autosomal recessive juvenile parkinsonism (AR-JP) characterized by selective dopaminergic neuronal death and absence of Lewy bodies. Recently we found that parkin is directly linked to the ubiquitin (Ub)-proteasome pathway as a Ub-protein ligase (E3) collaborating with a Ub-conjugating enzyme (E2) UbcH7. Here we analysed by in situ hybridization the expression of mRNAs for parkin and UbcR7 (rat orthologue of human UbcH7) in the developing rat brain. Parkin mRNA increased in parallel with neuronal maturation, but was unevenly distributed in various brain regions after four postnatal days. The expression pattern of the UbcR7 mRNA was almost identical to that of the parkin mRNA in all cases examined. Both parkin and UbcR7 mRNAs were distributed in neurones but not glial cells. Our findings indicate that parkin is expressed not only in the substantia nigra, but also uniformly in various brain regions in a development-dependent manner. Co-expression of UbcR7 with parkin suggests that UbcR7 may interact with parkin in vivo for ubiquitination of yet unidentified target protein(s).
帕金蛋白是Park2基因的产物,该基因的突变会导致常染色体隐性少年帕金森氏症(AR-JP),其特征为选择性多巴胺能神经元死亡且无路易小体。最近我们发现,帕金蛋白作为一种泛素(Ub)-蛋白连接酶(E3),与泛素结合酶(E2)UbcH7协同作用,直接与泛素(Ub)-蛋白酶体途径相关联。在此,我们通过原位杂交分析了发育中的大鼠大脑中帕金蛋白和UbcR7(人类UbcH7的大鼠同源物)的mRNA表达。帕金蛋白mRNA的增加与神经元成熟同步,但在出生后四天后在不同脑区分布不均。在所有检测的情况下,UbcR7 mRNA的表达模式与帕金蛋白mRNA的表达模式几乎相同。帕金蛋白和UbcR7 mRNA均分布于神经元而非神经胶质细胞中。我们的研究结果表明,帕金蛋白不仅在黑质中表达,而且在不同脑区以发育依赖的方式均匀表达。UbcR7与帕金蛋白的共表达表明,UbcR7可能在体内与帕金蛋白相互作用,以泛素化尚未确定的靶蛋白。