Dresbach Thomas, Hempelmann Anne, Spilker Christina, tom Dieck Susanne, Altrock Wilko D, Zuschratter Werner, Garner Craig C, Gundelfinger Eckart D
Leibniz Institute for Neurobiology, Brenneckestrasse 6, D-39118, Magdeburg, Germany.
Mol Cell Neurosci. 2003 Jun;23(2):279-91. doi: 10.1016/s1044-7431(03)00015-0.
Exocytosis of neurotransmitter from synaptic vesicles is restricted to specialized sites of the presynaptic plasma membrane called active zones. A complex cytomatrix of proteins exclusively assembled at active zones, the CAZ, is thought to form a molecular scaffold that organizes neurotransmitter release sites. Here, we have analyzed synaptic targeting and cytomatrix association of Bassoon, a major scaffolding protein of the CAZ. By combining immunocytochemistry and transfection of cultured hippocampal neurons, we show that the central portion of Bassoon is crucially involved in synaptic targeting and CAZ association. An N-terminal region harbors a distinct capacity for N-myristoylation-dependent targeting to synaptic vesicle clusters, but is not incorporated into the CAZ. Our data provide the first experimental evidence for the existence of distinct functional regions in Bassoon and suggest that a centrally located CAZ targeting function may be complemented by an N-terminal capacity for targeting to membrane-bounded synaptic organelles.
神经递质从突触小泡的胞吐作用局限于突触前质膜的特化部位，即活性区。一种专门在活性区组装的复杂蛋白质细胞基质，即CAZ，被认为形成了一个组织神经递质释放位点的分子支架。在这里，我们分析了CAZ的主要支架蛋白巴松管（Bassoon）的突触靶向和细胞基质关联。通过结合免疫细胞化学和培养海马神经元的转染，我们表明巴松管的中央部分在突触靶向和CAZ关联中起着关键作用。一个N端区域具有独特的能力，可通过N-肉豆蔻酰化依赖的方式靶向突触小泡簇，但不整合到CAZ中。我们的数据为巴松管中存在不同功能区域提供了首个实验证据，并表明位于中央的CAZ靶向功能可能由N端靶向膜结合突触细胞器的能力所补充。
