Differential abilities of SNAP-25 homologs to support neuronal function
Differential abilities of SNAP-25 homologs to support neuronal function
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DOI：
10.1523/jneurosci.5092-06.2007
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发表时间：
2007-08-29
影响因子：
5.3
通讯作者：
Sorensen, Jakob B.
中科院分区：
文献类型：
--
作者：
Delgado-Martinez, Ignacio;Nehring, Ralf B.;Sorensen, Jakob B.
SNAP受体（SNARE）复合物由25 kDa的突触体相关蛋白（SNAP-25）、小突触泡蛋白-2和突触融合蛋白-1组成，参与突触囊泡的胞吐作用。此外，SNAP-25还参与了神经突生长所需的组成性胞吐过程。然而，至少有三种SNAP-25的同种型已被报道来自神经元：SNAP-23，其也存在于非神经元细胞中，以及两种选择性剪接变体SNAP-25a和SNAP-25b。在这里，我们研究了这些异构体的差异能力，以支持以前广泛归因于"SNAP-25"的功能。“我们研究了在不同SNAP-25同源物的培养物中拯救SNAP-25无效神经元。我们发现SNAP-25的缺失会导致神经元存活率大幅降低，并且在少数存活细胞中，会损害树枝状结构、减少自发释放并完全阻止诱发释放。慢病毒表达SNAP-25a、SNAP-25b或SNAP-23拯救了神经元存活、树枝状化、幅度和自发事件的频率。诱发释放也被所有亚型拯救，但同步释放需要在谷氨酸能和GABA能神经元中的SNAP-25 a/B。SNAP-23只支持异步释放，让人想起synaptotagmin-1空神经元。SNAP-25 b是上级SNAP-25 a在囊泡启动，类似的转变，伴随着突触成熟的更大的可释放囊泡池。这些数据证明了SNAP-25b、SNAP-25a和SNAP-23支持神经元功能的不同能力。
The SNAP receptor ( SNARE) complex, consisting of synaptosome-associated protein of 25 kDa ( SNAP-25), synaptobrevin-2, and syntaxin-1, is involved in synaptic vesicles exocytosis. In addition, SNAP-25 has been implicated in constitutive exocytosis processes required for neurite outgrowth. However, at least three isoforms of SNAP-25 have been reported from neurons: SNAP-23, which is also present in non-neuronal cells, and the two alternative splice variants SNAP-25a and SNAP-25b. Here, we studied the differential ability of these isoforms to support the functions previously broadly ascribed to "SNAP-25." We studied the rescue of snap-25 null neurons in culture with different SNAP-25 homologs. We find that deletion of SNAP-25 leads to strongly reduced neuron survival, and, in the few surviving cells, impaired arborization, reduced spontaneous release, and complete arrest of evoked release. Lentiviral expression of SNAP-25a, SNAP-25b, or SNAP-23 rescued neuronal survival, arborization, amplitude, and frequency of spontaneous events. Also evoked release was rescued by all isoforms, but synchronous release required SNAP-25a/b in both glutamatergic and GABAergic neurons. SNAP-23 supported asynchronous release only, reminiscent of synaptotagmin-1 null neurons. SNAP-25b was superior to SNAP-25a in vesicle priming, resembling the shift to larger releasable vesicle pools that accompanies synaptic maturation. These data demonstrate a differential ability of SNAP-25b, SNAP-25a, and SNAP-23 to support neuronal function.