Müller B M, Kistner U, Veh R W, Cases-Langhoff C, Becker B, Gundelfinger E D, Garner C C
Center for Molecular Neurobiology, University of Hamburg, Germany.
J Neurosci. 1995 Mar;15(3 Pt 2):2354-66. doi: 10.1523/JNEUROSCI.15-03-02354.1995.
Synapses are highly specialized sites of cell-cell contact involved in signal transfer. The molecular mechanisms modulating the assembly and stability of synapses are unknown. We previously reported the identification of a 90 kDa synapse-associated protein, SAP90, that is localized at the presynaptic termini of inhibitory GABAergic synapses. SAP90 is a mosaic protein composed of three 90 amino acid residue repeats, an SH3 domain and a region homologous to guanylate kinases. SAP90 shares domain specific homology with a family of proteins involved in the assembly and possibly stability of sites of cell contact. These include the product of the lethal(1) discs-large-1 (dlgA) tumor suppressor gene and the zonula occludens proteins ZO-1, ZO-2. The further characterization of cDNA clones encoding components of synaptic junctions has lead to the identification of a 97 kDa protein, called SAP97, that exhibits a strong overall sequence similarity to SAP90. The present study was undertaken to determine the spatial distribution of SAP97, and to reveal further clues to the possible roles of these proteins in synapses. Light and immunoelectron microscopic analysis of the rat hippocampal formation revealed that SAP97 is localized in the presynaptic nerve termini of excitatory synapses. In other brain regions, SAP97 is found in and along bundles of unmyelinated axons. SAP97 is not restricted to the CNS, but is also present at the basal lateral membrane between a variety of epithelial cells. In cultured T84 cells, it is restricted to the cytoplasmic surface of the plasma membranes between adjacent cells, but not at the edges of cells lacking cell-cell contact suggesting a role for SAP97 in cell adhesion. These data suggest that members of the SAP90/SAP97 subfamily may be involved in the site specific assembly, stability or functions of membrane specialization at sites of cell-cell contact.
突触是参与信号传递的高度特化的细胞间接触位点。调节突触组装和稳定性的分子机制尚不清楚。我们先前报道了一种90 kDa突触相关蛋白SAP90的鉴定，该蛋白定位于抑制性GABA能突触的突触前末端。SAP90是一种镶嵌蛋白，由三个90个氨基酸残基的重复序列、一个SH3结构域和一个与鸟苷酸激酶同源的区域组成。SAP90与参与细胞接触位点组装及可能的稳定性的一类蛋白具有结构域特异性同源性。这些蛋白包括致死（1）盘大-1（dlgA）肿瘤抑制基因的产物以及紧密连接蛋白ZO-1、ZO-2。对编码突触连接成分的cDNA克隆的进一步表征导致鉴定出一种97 kDa的蛋白，称为SAP97，它与SAP90具有很强的整体序列相似性。本研究旨在确定SAP97的空间分布，并揭示这些蛋白在突触中可能作用的更多线索。对大鼠海马结构的光镜和免疫电镜分析表明，SAP97定位于兴奋性突触的突触前神经末端。在其他脑区，SAP97存在于无髓轴突束中及其周围。SAP97不仅局限于中枢神经系统，还存在于多种上皮细胞之间的基底外侧膜上。在培养的T84细胞中，它局限于相邻细胞之间质膜的胞质表面，但不存在于缺乏细胞间接触的细胞边缘，这表明SAP97在细胞黏附中起作用。这些数据表明，SAP90/SAP97亚家族成员可能参与细胞间接触位点膜特化的位点特异性组装、稳定性或功能。
