Reference Report

Reference
Citation	Shao, L., Shuai, Y., Wang, J., Feng, S., Lu, B., Li, Z., Zhao, Y., Wang, L., Zhong, Y. (2011). Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 108(46): 18831--18836. (Export to RIS)
FlyBase ID	FBrf0216775
Publication Type	Research paper
PubMed ID	22049342
PubMed Abstract	The dysfunction of multiple neurotransmitter systems is a striking pathophysiological feature of many mental disorders, schizophrenia in particular, but delineating the underlying mechanisms has been challenging. Here we show that manipulation of a single schizophrenia susceptibility gene, dysbindin, is capable of regulating both glutamatergic and dopaminergic functions through two independent mechanisms, consequently leading to two categories of clinically relevant behavioral phenotypes. Dysbindin has been reported to affect glutamatergic and dopaminergic functions as well as a range of clinically relevant behaviors in vertebrates and invertebrates but has been thought to have a mainly neuronal origin. We find that reduced expression of Drosophila dysbindin (Ddysb) in presynaptic neurons significantly suppresses glutamatergic synaptic transmission and that this glutamatergic defect is responsible for impaired memory. However, only the reduced expression of Ddysb in glial cells is the cause of hyperdopaminergic activities that lead to abnormal locomotion and altered mating orientation. This effect is attributable to the altered expression of a dopamine metabolic enzyme, Ebony, in glial cells. Thus, Ddysb regulates glutamatergic transmission through its neuronal function and regulates dopamine metabolism by regulating Ebony expression in glial cells.
DOI	10.1073/pnas.1114569108
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Proc. Natl. Acad. Sci. U.S.A.
Title	Proceedings of the National Academy of Sciences of the United States of America
Publication Year	1915-
ISBN/ISSN	0027-8424
Data from Reference
Alleles (15)
	dysb^e01028 dysb^{NIG.IR-6856R-1} dysb^{NIG.IR-6856R-2} dysb^Scer\UAS.cSa dysb^{Scer\UAS.T:Avic\GFP-YFP.Venus} e¹ Hsap\DTNBP1^Scer\UAS.cSa Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Scer\GAL4^Act5C.PI Scer\GAL4^C57 Scer\GAL4^elav-C155 Scer\GAL4^hs.PU Scer\GAL4^NP3233 Scer\GAL4^repo Scer\GAL4^VGlut-OK371
Constructs (8)
	P{Act5C-GAL4} P{hs-GAL4.U} P{NIG.6856R-1} P{NIG.6856R-2} P{UAS-DTNBP1.S} P{UAS-dysb.S} P{UAS-dysb.ven} P{UAS-mCD8::GFP.L}
Genes (7)
	dysb e Hsap\DTNBP1 Mmus\Cd8a ple Scer\GAL4 tan
Insertions (5)
	P{GAL4}repo P{GawB}C57 P{GawB}elav^C155 P{GawB}NP3233 P{GawB}VGlut^OK371
Natural transposons (1)
	P-element