The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles
The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles
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DOI：
10.1083/jcb.201301072
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发表时间：
2013-08-19
影响因子：
7.8
通讯作者：
Sigrist, Stephan J.
中科院分区：
文献类型：
--
作者：
Matkovic, Tanja;Siebert, Matthias;Sigrist, Stephan J.
突触小泡(SVS)融合在一个特殊的膜域，称为活动区(AZ)，被保守的细胞线覆盖。Cytomatrix组分是如何与SV释放相交的，目前还不够清楚。我们之前已经证明，失去果蝇黑腹果蝇ELKS家族蛋白BruchPilot(BRP)会消除细胞基质(T Bar)，并破坏钙通道。在本文中，我们从两种BRP亚型的生化鉴定入手，探索了Cytomatrix的附加功能。这两种异构体在环形阵列中交替，对于正确的T-bar形成是重要的。在异构体特异性突变体中，基础传递率降低，我们将其归因于SVS易释放池(RRP)的大小减少。我们还发现，停靠在剩余细胞基质附近的SVS数量也相应减少。我们认为，由BRP异构体的交替模式创建的大分子结构决定了每个AZ可用的钙通道偶联SV释放槽的数量，从而决定了RRP的大小。
Synaptic vesicles (SVs) fuse at a specialized membrane domain called the active zone (AZ), covered by a conserved cytomatrix. How exactly cytomatrix components intersect with SV release remains insufficiently understood. We showed previously that loss of the Drosophila melanogaster ELKS family protein Bruchpilot (BRP) eliminates the cytomatrix (T bar) and declusters Ca2+ channels. In this paper, we explored additional functions of the cytomatrix, starting with the biochemical identification of two BRP isoforms. Both isoforms alternated in a circular array and were important for proper T-bar formation. Basal transmission was decreased in isoform-specific mutants, which we attributed to a reduction in the size of the readily releasable pool (RRP) of SVs. We also found a corresponding reduction in the number of SVs docked close to the remaining cytomatrix. We propose that the macromolecular architecture created by the alternating pattern of the BRP isoforms determines the number of Ca2+ channel-coupled SV release slots available per AZ and thereby sets the size of the RRP.