Facchiano F, Benfenati F, Valtorta F, Luini A
Laboratory of Molecular Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri, S. Maria Imbaro, Chieti, Italy.
J Biol Chem. 1993 Mar 5;268(7):4588-91.
The synapsins are neuronal phosphoproteins that bind to small synaptic vesicles and to actin filaments and are believed to play a regulatory role in neurotransmitter release. Here we show that synapsin I is covalently modified with remarkable affinity and selectivity by the enzyme transglutaminase. Transglutaminase catalyzes the formation of covalent bonds between protein glutamine residues and primary amines and has been found recently to be potently activated by tetanus toxin, a dichain clostridial protein that selectively blocks neurotransmitter secretion. We also report the presence of two species of immunoreactive transglutaminases in nerve endings, one cytosolic and one located on synaptic vesicles; they are potently activated by tetanus toxin and, when activated, covalently modify synaptic vesicle-bound synapsin I. These results suggest a role for transglutaminase in the control of neurotransmitter secretion and provide evidence for synapsin I being a molecular target of tetanus toxin.
突触结合蛋白是一种神经元磷蛋白，它能与小突触囊泡及肌动蛋白丝结合，据信在神经递质释放过程中发挥调节作用。在此我们表明，转谷氨酰胺酶能以显著的亲和力和选择性对突触结合蛋白I进行共价修饰。转谷氨酰胺酶催化蛋白质谷氨酰胺残基与伯胺之间形成共价键，最近发现它可被破伤风毒素强烈激活，破伤风毒素是一种双链梭菌蛋白，能选择性地阻断神经递质分泌。我们还报告了在神经末梢存在两种免疫反应性转谷氨酰胺酶，一种位于胞质溶胶中，另一种位于突触囊泡上；它们可被破伤风毒素强烈激活，激活后会对与突触囊泡结合的突触结合蛋白I进行共价修饰。这些结果表明转谷氨酰胺酶在神经递质分泌控制中发挥作用，并为突触结合蛋白I是破伤风毒素的分子靶点提供了证据。
