title: Covalent modification of synapsin I by a tetanus toxin-activated transglutaminase.
abstract: 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.
authors.affiliation: Laboratory of Molecular Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri, S. Maria Imbaro, Chieti, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Facchiano
authors.forename: F
authors.initials: F
authors.lastname: Benfenati
authors.forename: F
authors.initials: F
authors.lastname: Valtorta
authors.forename: A
authors.initials: A
authors.lastname: Luini
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D016704:Synapsins / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D013744:Tetanus Toxin / Q000494:pharmacology*; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D016704:Synapsins; D013744:Tetanus Toxin; D011503:Transglutaminases; D002118:Calcium