Calpain-mediated regulation of stargazin in adult rat brain.
Calpain-mediated regulation of stargazin in adult rat brain.
复制标题
成年大鼠大脑中钙蛋白酶介导的观星调节。
DOI：
10.1016/j.neuroscience.2011.01.026
复制
发表时间：
2011
期刊：
影响因子：
3.3
通讯作者：
Baudry,M
中科院分区：
文献类型：
--
作者：
Yu,L;Rostamiani,K;Hsu,Y-T;Wang,Y;Bi,X;Baudry,M
AMPA受体的变化被认为是海马体和其他脑结构突触效能变化的基础。钙蛋白酶的激活也被认为是产生突触结构和功能持久改变的潜在机制。Stargazin是跨膜型AMPA受体相关蛋白(TARP)家族的成员，参与AMPA受体的转运并调节其动力学特性。我们在此报道，将薄的(20μm)冷冻大鼠脑片与钙预先孵育会改变Stargazin的免疫学特性，这一作用可被Calain抑制剂完全阻断。免疫细胞化学显示，在整个大脑的神经束中，原位的calain激活会导致Stargazin的免疫反应性降低，而Western blotts证实，类似的处理降低了Stargazin的水平。有趣的是，同样的处理并没有改变另一种TARP成员γ-8的免疫反应性，尽管它增加了海马体中的免疫反应性，这一效应不会被Calain抑制所阻断。这些结果有力地表明，Calain通过截断Stargazin参与调节AMPA受体的靶向性和功能。
Changes in AMPA receptors have been proposed to underlie changes in synaptic efficacy in hippocampus and other brain structures. Calpain activation has also been discussed as a potential mechanism to produce lasting modifications of synaptic structure and function. Stargazin is a member of the family of transmembrane AMPA receptor associated proteins (TARPs), which participates in trafficking of AMPA receptors and regulates their kinetic properties. We report here that preincubation of thin (20 μm) frozen rat brain sections with calcium changes the immunological properties of stargazin, an effect totally blocked by a calpain inhibitor. Immunocytochemistry indicates that in situ calpain activation produces a decreased immunoreactivity for stargazin in the neuropil throughout the brain, and Western blots confirmed that a similar treatment decreased stargazin levels. Interestingly, the same treatment did not modify the immunoreactivity for another TARP member, γ-8, although it increased immunoreactivity in cell bodies in hippocampus, an effect that was not blocked by calpain inhibition. These results strongly suggest the involvement of calpain in the regulation of AMPA receptor targeting and function through truncation of stargazin.