Differential distributions of the Ca2+-dependent activator protein for secretion family proteins (CAPS2 and CAPS1) in the mouse brain

Differential distributions of the Ca2+-dependent activator protein for secretion family proteins (CAPS2 and CAPS1) in the mouse brain
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DOI:
10.1002/cne.20947
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发表时间:
2006-04-20
影响因子:
2.5
通讯作者:
Furuichi, T
Furuichi, T
中科院分区:
医学3区
文献类型:
--
作者:
Sadakata, T;Itakura, M;Furuichi, T

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Ca 2+依赖性分泌激活蛋白(CAPS/Cadps)家族由CAPS 1和CAPS 2两个成员组成,在分泌颗粒胞吐中起重要作用。研究表明,CAPS 1调节神经内分泌细胞释放的儿茶酚胺,而CAPS 2参与小脑颗粒细胞平行纤维释放的两种神经营养因子,脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)。虽然这两种CAPS蛋白主要在脑中表达,但它们在脑中的细胞和区域分布在很大程度上是未知的。在这项研究中,我们分析了CAPS家族蛋白在小鼠脑中的免疫组织化学分布。在胚胎神经系统的大部分区域,CAPS 1和CAPS 2蛋白互补表达。在出生后的大脑中,CAPS 1广泛分布在不同的水平。另一方面,CAPS 2定位于不同的细胞类型和不同的大脑区域的纤维,包括嗅球,大脑,海马结构,丘脑,中脑被盖,小脑,髓质和脊髓,除了一些区域与CAPS 1重叠。CAPS 2在各脑区的分布与BDNF的分布具有明显的一致性。CAPS 2的免疫标记也与细胞索马和中脑被盖和小脑的过程中的胞吐作用(VAMP和SNAP-25)和胞吞作用(发动蛋白I)相关的一些蛋白质共定位,这表明这些蛋白质可能参与CAPS 2相关囊泡的动力学,尽管它们在囊泡上的共定位仍然难以捉摸。这些结果表明,CAPS家族蛋白参与了发育和出生后大脑中不同分泌物质的分泌,并且CAPS 2可能参与了许多脑区域的BDNF分泌。
The Ca2+-dependent activator protein for secretion (CAPS/Cadps) family consists of two members, CAPS1 and CAPS2, and plays an important role in secretory granule exocytosis. It has been shown that CAPS1 regulates catecholamine release from neuroendocrine cells, whereas CAPS2 is involved in the release of two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), from parallel fibers of cerebellar granule cells. Although both CAPS proteins are expressed predominantly in the brain, their cellular and regional distributions in the brain are largely unknown. In this study we analyzed the immunohistochemical distributions of the CAPS family proteins in the mouse brain. In most areas of the embryonic nervous system CAPS1 and CAPS2 proteins were complementarily expressed. In the postnatal brain, CAPS1 was widespread at different levels. On the other hand, CAPS2 was localized to distinct cell types and fibers of various brain regions, including the olfactory bulb, cerebrum, hippocampal formation, thalamus, mesencephalic tegmentum, cerebellum, medulla, and spinal cord, except for some regions that overlapped with CAPS1. These CAPS2 cellular distribution patterns had the marked feature of coinciding with those of BDNF in various brain regions. Immunolabels for CAPS2 were also colocalized with those for some proteins related to exocytosis (VAMP and SNAP-25) and endocytosis (Dynamin I) in the cell soma and processes of the mesencephalic tegmentum and cerebellum, suggesting that these proteins might be involved in the dynamics of CAPS2-associated vesicles, although their colocalization on vesicles remains elusive. These results demonstrate that the CAPS family proteins are involved in the secretion of different secretory substances in developing and postnatal brains, and that CAPS2 is probably involved in BDNF secretion in many brain areas.