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大细胞性血管加压素分泌神经元中胞体和树突的功能:超微结构研究的新见解

Functions of the perikaryon and dendrites in magnocellular vasopressin-secreting neurons: new insights from ultrastructural studies.

作者信息

Morris J F, Budd T C, Epton M J, Ma D, Pow D V, Wang H

机构信息

Department of Human Anatomy, University of Oxford, UK.

出版信息

Prog Brain Res. 1998;119:21-30. doi: 10.1016/s0079-6123(08)61559-9.

Abstract

Magnocellular hypothalamic neurosecretory neurons secreting vasopressin or oxytocin provide a robust model system for the investigation and understanding of many aspects of peptidergic neuronal function. Many of their functions and the cellular organelles involved are well understood. However, recent ultrastructural studies have thrown new light on various aspects of magnocellular neurosecretory function which have not previously received much attention. This review concerns two of these: the effects of mutations in the vasopressin gene on the handling of the translated peptide by the rough endoplasmic reticulum; and the role of the magnocellular dendrites in the production, secretion and localisation of peptides. Investigation of the synthesis of proteins derived from vasopressin genes which have undergone various mutations has at the moment provided more answers than questions: Why do some abnormal products accumulate as masses of peptide in the rough endoplasmic reticulum while others do not? Why do accumulations in humans appear to be damaging to the neurons while those in the rat do not? Investigations of the role of dendrites in the production and release of peptides show that the dendrites have all the machinery needed for protein translation and appear to synthesize locally proteins required for dendritic function. Of particular interest is the possibility that various transmitter receptor proteins could be synthesized in the dendrites close to the synapses in which they become localized. Precisely how such membrane proteins are inserted into the synaptic complex is, however, unclear, because the most part of the dendrites lack any form of the Golgi packaging organelle that can be recognised as such either by immunocytochemistry or electron microscopy. Better established is the ability of magnocellular dendrites to secrete either vasopressin or oxytocin in response to a variety of stimuli including sex steroids. This local release of peptide into the magnocellular nuclei has important but as yet incompletely defined effects on the functioning of the neurons.

摘要

分泌抗利尿激素或催产素的下丘脑大细胞神经分泌神经元,为研究和理解肽能神经元功能的诸多方面提供了一个强大的模型系统。它们的许多功能以及所涉及的细胞器已为人熟知。然而,最近的超微结构研究为大细胞神经分泌功能的各个方面带来了新的启示,而这些方面此前并未受到太多关注。本综述涉及其中两个方面:抗利尿激素基因突变对粗面内质网处理翻译后肽段的影响;以及大细胞树突在肽的产生、分泌和定位中的作用。目前,对经历各种突变的抗利尿激素基因衍生蛋白质合成的研究提供的答案多于问题:为什么一些异常产物会以肽团的形式在粗面内质网中积累,而其他产物则不会?为什么人类中的积累似乎会损害神经元,而大鼠中的积累则不会?对树突在肽的产生和释放中作用的研究表明,树突具备蛋白质翻译所需的所有机制,并且似乎能在局部合成树突功能所需的蛋白质。特别令人感兴趣的是,各种递质受体蛋白有可能在其定位的突触附近的树突中合成。然而,目前尚不清楚这些膜蛋白究竟是如何插入突触复合体的,因为大部分树突缺乏任何形式的高尔基体包装细胞器,无论是通过免疫细胞化学还是电子显微镜都无法识别。大细胞树突对包括性类固醇在内的多种刺激作出反应,分泌抗利尿激素或催产素的能力则已得到更充分的确立。肽向大细胞核的这种局部释放对神经元的功能具有重要但尚未完全明确的影响。

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