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肌成纤维细胞关联蛋白(SPARC)阻止胆碱能突触前末端的成熟。

SPARC prevents maturation of cholinergic presynaptic terminals.

机构信息

Laboratori de Neurobiologia, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Spain.

出版信息

Mol Cell Neurosci. 2012 Mar;49(3):364-74. doi: 10.1016/j.mcn.2012.01.005. Epub 2012 Jan 25.

DOI:10.1016/j.mcn.2012.01.005
PMID:22306863
Abstract

Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein produced by glial cells. Although it is highly expressed in synaptogenic areas in the developing nervous system, it is still unclear whether this molecule displays an action on synaptic activity. We show that nanomolar concentrations of SPARC favour a more efficient synapse formation and increase short term depression in single cell cholinergic microcultures. The change in synaptic plasticity, which is also observed when SPARC is locally secreted on stable synapses for 24-48 h, is caused by a high release probability and a reduction in the size of the rapidly releasable pool of vesicles. Both features are attributable to synapses operating at an immature stage as demonstrated by correlative electrophysiology and electron microscopy experiments. Presynaptic terminals developed in the presence of SPARC display few cytoplasmic vesicles and two to threefold decrease in the number of docked vesicles at active zones. At the postsynaptic level, the analysis of miniature excitatory postsynaptic currents suggests SPARC has little effect on the number of nicotinic receptors but might alter their composition. The widespread distribution of SPARC makes current findings potentially relevant to other excitatory synapses and development of neuronal circuits.

摘要

富含半胱氨酸的酸性分泌蛋白(SPARC)是一种由神经胶质细胞产生的细胞外基质蛋白。虽然它在发育中的神经系统的突触形成区高度表达,但目前尚不清楚该分子是否对突触活动有作用。我们发现,纳摩尔浓度的 SPARC 有利于更有效的突触形成,并增加单细胞胆碱能微培养物中的短期抑郁。这种突触可塑性的变化,当 SPARC 在稳定的突触上局部分泌 24-48 小时时也会观察到,是由于高释放概率和快速释放池囊泡的减少引起的。这两个特征都归因于在电生理学和电子显微镜实验中证明的处于不成熟阶段的突触。在 SPARC 存在的情况下发育的突触前末端显示出很少的细胞质囊泡,并且在活性区的停靠囊泡数量减少了两到三倍。在突触后水平,对微小兴奋性突触后电流的分析表明 SPARC 对烟碱型受体的数量几乎没有影响,但可能改变它们的组成。SPARC 的广泛分布使得当前的发现可能与其他兴奋性突触和神经元回路的发育有关。

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