Calcium-dependent activator protein for secretion 2 is involved in dopamine release in mouse midbrain neurons

IF 3.5 3区医学 Q2 NEUROSCIENCES Frontiers in Molecular Neuroscience Pub Date : 2024-07-18 DOI:10.3389/fnmol.2024.1444629

Hirotoshi Iguchi, Takumi Katsuzawa, Chihiro Saruta, Tetsushi Sadakata, Shota Kobayashi, Yumi Sato, Akira Sato, Yoshitake Sano, So Maezawa, Yo Shinoda, Teiichi Furuichi

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Abstract

The Ca2+-dependent activator protein for secretion (CAPS/CADPS) family protein facilitates catecholamine release through the dense-core vesicle exocytosis in model neuroendocrine cell lines. However, it remains unclear if it induces dopamine release in the central neurons. This study aimed to examine the expression and function of CADPS2, one of the two CADPS paralogs, in dopamine neurons of the mouse midbrain. This study shows that CADPS2 was expressed in tyrosine hydroxylase and the vesicular monoamine transporter 2 (VMAT2)-positive dopaminergic neurons of the midbrain samples and primary mesencephalic cell cultures. Subcellular fractions rich in dopamine were collected using immunoaffinity for CADPS2 from midbrain protein extracts. Cell imaging using fluorescent false neurotransmitter FFN511 as a substrate for VMAT2 showed decreased activity-dependent dopamine release in Cadps2-deficient cultures, compared to that in wild-type cultures. These results suggest that CADPS2 is involved in dopamine release from the central neurons, indicating its involvement in the central dopamine pathway.

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钙依赖性分泌激活蛋白 2 参与小鼠中脑神经元多巴胺的释放

Ca2+ 依赖性分泌激活蛋白（CAPS/CADPS）家族蛋白可通过模型神经内分泌细胞系中的致密核心囊泡外泌作用促进儿茶酚胺的释放。然而，它是否能诱导中枢神经元释放多巴胺仍不清楚。本研究旨在检测两个 CADPS 旁系亲属之一的 CADPS2 在小鼠中脑多巴胺神经元中的表达和功能。研究表明，CADPS2在中脑样本和间脑原代细胞培养物中的酪氨酸羟化酶和囊泡单胺转运体2（VMAT2）阳性多巴胺能神经元中均有表达。利用中脑蛋白提取物中的 CADPS2 免疫亲和法收集富含多巴胺的亚细胞组分。使用荧光假神经递质 FFN511 作为 VMAT2 的底物进行的细胞成像显示，与野生型培养物相比，Cadps2 缺陷培养物中活动依赖性多巴胺释放量减少。这些结果表明，CADPS2 参与了中枢神经元的多巴胺释放，表明它参与了中枢多巴胺通路。

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.