Cellular dynamics of functional molecules and second messengers during synaptic transmission

肌醇高多磷酸系列（IP4， IP5和IP6； IHPS）通过结合突触塔蛋白（Syt）的第2 C2结构域，突触囊泡膜蛋白通过颈上神经节和鱿鱼巨突触抑制神经传递。现在，我们发现了几种蛋白质，包括网格蛋白AP2的特异性亚基α适应蛋白，用50muM的六磷酸肌醇（IP6）用亲和洗脱层析法从Syt ii -固定化Sepharose的C2结构域从小鼠脑中洗脱。与相同浓度的IP3相比，IHPS对Syt II与AP2相互作用的抑制作用更强。用胰蛋白酶对小鼠粗突触体进行有限消化，发现50muM - IP6存在时和不存在时的卵裂模式不同。这些结果表明，ihps结合到synaptotagmin的C2B结构域改变了蛋白-蛋白相互作用的状态，如synaptotagmin- ap2相互作用，这可能导致一些参与神经传递的事件，如内吞作用的抑制。

The inositol high-polyphodphate series (IP4, IP5 and IP6 ; IHPS) inhibit the neurotransmission through binding to the 2nd C2 domain of synaptotagmin (Syt), synaptic vesicle membrane proteins using superior cervical ganglion and squid giant synapse. Now we have revealed several proteins, including alpha adaptins which are specific subunits of clathrin AP2, from mouse brain were eluted by affinity elution chromatography from the C2 domain of Syt II-immobilized Sepharose using 50muM of inositol hexakisphosphate (IP6). The interaction between Syt II and AP2 was inhibited more strongly by IHPS than by the same concentration of IP3. Limited digestion of mouse crude synaptosomal fractions with trypsin revealed different cleavage pattern between in the presenc and the absence of 50muM IP6. These results suggests that IHPS-binding to C2B domain of synaptotagmin alter the state of protein-protein interaction such as synaptotagmin-AP2 interaction, which may induce the inhibition of some events involved in the neurotransmission, e.g. endocytosis.