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J. Biol. Chem., Vol. 275, Issue 47, 36920-36926, November 24, 2000
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From the Departments of Rat synaptotagmin IV (SYT IV) is a
depolarization-inducible synaptic vesicle protein. SYT IV homozygous
mutant mice are viable and have deficits in fine motor coordination and
some forms of memory. In this study, we report the identification of a
human SYT IV orthologue. The predicted amino acid sequence of the human SYT IV clone is nearly 90% identical to the rat and mouse SYT IV
proteins. In addition, human SYT IV has a characteristic serine for
aspartate substitution within the first C2 domain that is conserved
among Drosophila, Caenorhabditis elegans,
mouse, and rat SYT IV sequences. The human SYT IV
gene maps to chromosome band 18q12.3, a region that defines a break
point in the synteny with mouse chromosome 18 and has been implicated
by associated markers in two human psychiatric disorders. In the human
neuroblastoma cell line SK-N-SH, SYT IV is an
immediate-early gene inducible by elevated intracellular calcium and by
forskolin, an activator of adenylyl cyclase. Expression of human SYT IV
mRNA is restricted to brain and is not detectable in non-neuronal
tissues. Within brain, human SYT IV mRNA is most highly expressed
in hippocampus, with lower levels present in amygdala and thalamus.
These results suggest a role for SYT IV in human brain function and in
human neurological disease.
The Human Synaptotagmin IV Gene Defines an Evolutionary Break
Point between Syntenic Mouse and Human Chromosome Regions but Retains
Ligand Inducibility and Tissue Specificity*
§,
**
Biological Chemistry and
Pharmacology and the ** Molecular Biology Institute,
¶ Medical Genetics Birth Defects Center, Cedars-Sinai Medical
Center, UCLA, Los Angeles, California 90095
*
This work was supported in part by National Institutes of
Health Grants NS28660 (to H. R. H.), HD33113 (to J. R. K.), and HD17449 (to J. R. K.), the Geri and Richard Brawermen Chair for Molecular Genetics (to J. R. K.), and Department of Energy Grant DE-FG03-92ER-61402 (to J. R. K.).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 should be addressed: 341 Boyer Hall
(Molecular Biology Institute), UCLA, 611 Charles E. Young Dr., East,
Los Angeles, CA 90095. Tel.: 310-825-8735; Fax: 310-825-1447; E-mail:
hherschman@mednet.ucla.edu.
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  M. Fukuda and A. Yamamoto Effect of Forskolin on Synaptotagmin IV Protein Trafficking in PC12 Cells J. Biochem., August 1, 2004; 136(2): 245 - 253. [Abstract] [Full Text] [PDF]
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