Insulin-like growth factor-II/mannose-6-phosphate receptor: Widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype

Insulin-like growth factor-II/mannose-6-phosphate receptor: Widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype
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DOI:
10.1002/cne.10578
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发表时间:
2003-03-31
影响因子:
2.5
通讯作者:
Kar, S
Kar, S
中科院分区:
医学3区
文献类型:
--
作者:
Hawkes, C;Kar, S

文献摘要

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胰岛素样生长因子-II/甘露糖-6-磷酸(IGF-II/M6 P)受体是单跨膜糖蛋白,在溶酶体酶的运输和循环IGF-II的内化中起关键作用。目前,关于IGF-II/M6 P受体在成年大鼠脑内的细胞分布的信息很少。通过免疫印迹和免疫细胞化学方法,我们发现IGF-II/M6 P受体广泛但选择性地表达于所有主要脑区,包括嗅球、纹状体、皮质、海马、丘脑、下丘脑、小脑、脑干和脊髓。强烈的IGF-II/M6 P受体免疫反应性在纹状体内的神经元细胞体、皮质的深层(第IV和V层)、海马结构的锥体细胞和颗粒细胞层、选定的丘脑核、小脑的浦肯野细胞、脑桥核和脑干的运动神经元以及脊髓中明显。中度神经元标记在嗅球、基底前脑区、下丘脑、上级丘、中脑区、小脑颗粒细胞和脊髓灰质的中间区域中是明显的。我们还观察到在许多区域中的密集的neurology标记,表明该受体定位于树突和/或轴突终末。双标记研究进一步表明,IGF-II/M6 P受体的一个子集与隔,纹状体,斜角带复合体,基底核,皮质,海马和脑干和脊髓的运动神经元中的胆碱能细胞体和纤维共定位。IGF-II/M6 P受体在成年大鼠脑中的广泛分布和共定位提供了一个解剖学基础,表明受体在广谱中枢神经系统神经元(包括表达胆碱能表型的神经元)中具有多功能作用。
The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is single transmembrane glycoprotein that plays a critical role in the trafficking of lysosomal enzymes and the internalization of circulating IGF-II. At present, there is little information regarding the cellular distribution of the IGF-II/M6P receptor within the adult rat brain. With the use of immunoblotting and immunocytochemical methods, we found that the IGF-II/M6P receptor is widely but selectively expressed in all major brain areas, including the olfactory bulb, striatum, cortex, hippocampus, thalamus, hypothalamus, cerebellum, brainstem, and spinal cord. Intense IGF-II/M6P receptor immunoreactivity was apparent on neuronal cell bodies within the striatum, deeper layers (layers IV and V) of the cortex, pyramidal and granule cell layers of the hippocampal formation, selected thalamic nuclei, Purkinje cells of the cerebellum, pontine nucleus and motoneurons of the brainstem as well as in the spinal cord. Moderate neuronal labeling was evident in the olfactory bulb, basal forebrain areas, hypothalamus, superior colliculus, midbrain areas, granule cells of the cerebellum and in the intermediate regions of the spinal gray matter. We also observed dense neuropil labeling in many regions, suggesting that this receptor is localized in dendrites and/or axon terminals. Double-labeling studies further indicated that a subset of IGF-II/M6P receptor colocalizes with cholinergic cell bodies and fibers in the septum, striatum, diagonal band complex, nucleus basalis, cortex, hippocampus, and motoneurons of the brainstem and spinal cord. The observed widespread distribution and colocalization of IGF-II/ M6P receptor in the adult rat brain provide an anatomic basis to suggest a multifunctional role for the receptor in a wide-spectrum of central nervous system neurons, including those expressing a cholinergic phenotype.