Telencephalin slows spine maturation
Telencephalin slows spine maturation
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DOI：
10.1523/jneurosci.2651-05.2006
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发表时间：
2006-02-08
影响因子：
5.3
通讯作者：
Yoshihara, Y
中科院分区：
文献类型：
--
作者：
Matsuno, H;Okabe, S;Yoshihara, Y
树突丝状足是高度动态的结构，从树突丝状足到棘的形态成熟与发育过程中突触的稳定和加强密切相关。在这里，我们报道了端脑蛋白（TLCN），一种属于Ig超家族的细胞粘附分子，是脊柱成熟的负调节因子。利用培养的海马神经元，我们详细研究了TLCN在脊柱发育和突触发生中的定位和功能。在突触发生早期，TLCN免疫反应性逐渐增强，并出现在树突轴和丝状足。在后期阶段，TLCN倾向于被排除在成熟的脊柱突触之外，其中PSD-95（突触后密度-95）簇与突触前突触体素簇相对。为了阐明TLCN在脊柱成熟中的作用，我们分析了TLCN过表达和TLCN缺失神经元的树突形态。TLCN的过度表达引起树突丝状足密度的急剧增加，同时引起棘密度的减少。相反，tlcn缺陷小鼠在体外和体内均表现出丝足密度下降和脊柱成熟加速。这些结果表明，TLCN通常通过促进丝状足形成和负调控丝状足到脊柱的转变来减缓脊柱成熟。此外，我们发现tlcn缺陷小鼠的成熟神经元棘头比野生型小鼠更宽。因此，TLCN对未成熟突触的保存可能是完善端脑功能神经回路的必要步骤，端脑负责高级脑功能，如学习、记忆和情感。
Dendritic filopodia are highly dynamic structures, and morphological maturation from dendritic filopodia to spines is intimately associated with the stabilization and strengthening of synapses during development. Here, we report that telencephalin (TLCN), a cell adhesion molecule belonging to the Ig superfamily, is a negative regulator of spine maturation. Using cultured hippocampal neurons, we examined detailed localization and functions of TLCN in spine development and synaptogenesis. At early stages of synaptogenesis, TLCN immunoreactivity gradually increased and was present in dendritic shafts and filopodia. At later stages, TLCN tended to be excluded from mature spine synapses in which PSD-95 (postsynaptic density-95) clusters were apposed to presynaptic synaptophysin clusters. To elucidate the function of TLCN in spine maturation, we analyzed the dendrite morphology of TLCN-overexpressing and TLCN-deficient neurons. Overexpression of TLCN caused a dramatic increase in the density of dendritic filopodia and a concomitant decrease in the density of spines. Conversely, TLCN-deficient mice showed a decreased density of filopodia and an acceleration of spine maturation in vitro as well as in vivo. These results demonstrate that TLCN normally slows spine maturation by promoting the filopodia formation and negatively regulating the filopodia-to-spine transition. In addition, we found that spine heads of mature neurons were wider in TLCN-deficient mice compared with wild-type mice. Thus, the preservation of immature synapses by TLCN may be an essential step for refinement of functional neural circuits in the telencephalon, that take charge of higher brain functions such as learning, memory, and emotion.