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J. Biol. Chem., Vol. 277, Issue 33, 30351-30358, August 16, 2002
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From the Fukuda Initiative Research Unit, RIKEN (The Institute of
Physical and Chemical Research), 2-1 Hirosawa, Wako,
Saitama 351-0198, Japan
Synaptotagmin I (Syt I), an evolutionarily
conserved integral membrane protein of synaptic vesicles, is now known
to regulate Ca2+-dependent
neurotransmitter release. Syt I protein should undergo several
post-translational modifications before maturation and subsequent
functioning on synaptic vesicles (e.g.
N-glycosylation and fatty acylation in vertebrate Syt I),
because the apparent molecular weight of Syt I on synaptic vesicles
(mature form, 65,000) was much higher than the calculated molecular
weight (47,400) predicted from the cDNA sequences both in
vertebrates and invertebrates. Common post-translational
modification(s) of Syt I conserved across phylogeny, however, have
never been elucidated. In the present study, I discovered that
dithreonine residues (Thr-15 and Thr-16) at the intravesicular domain
of mouse Syt I are post-translationally modified by a complex form of
O-linked sugar (i.e. the addition of sialic
acids) in PC12 cells and that the O-glycosylation of Syt
I in COS-7 cells depends on the coexpression of vesicle-associated membrane protein-2 (VAMP-2)/synaptobrevin. I also showed that a
transmembrane domain of Syt I directly interacts with isolated VAMP-2,
but not VAMP-2, in the heterotrimeric SNARE (SNAP
receptor) complex (vesicle SNARE, VAMP-2, and two target
SNAREs, syntaxin IA and SNAP-25). Since di-Thr or di-Ser residues are
often found at the intravesicular domain of invertebrate Syt I, and
VAMP-dependent O-glycosylation was also
observed in squid Syt expressed in COS-7 cells, I propose that
VAMP-dependent O-glycosylation of Syt I is a
common modification during evolution and may have important role(s) in
synaptic vesicle trafficking.
Vesicle-associated Membrane Protein-2/Synaptobrevin Binding to
Synaptotagmin I Promotes O-Glycosylation of Synaptotagmin
I*
*
This work was supported in part by grants from the Science
and Technology Agency of Japan (to M. F.) and Grant 13780624 from the
Ministry of Education, Science, and Culture of Japan (to M. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed. Tel.: 81-48-462-4994;
Fax: 81-48-462-4995; E-mail: mnfukuda@brain.riken.go.jp.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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