@article {46605,
	title = {DlgS97/SAP97, a neuronal isoform of discs large, regulates ethanol tolerance.},
	journal = {PLoS One},
	volume = {7},
	year = {2012},
	month = {2012 Nov 7},
	pages = {e48967},
	abstract = {<p>From a genetic screen for Drosophila melanogaster mutants with altered ethanol tolerance, we identified intolerant (intol), a novel allele of discs large 1 (dlg1). Dlg1 encodes Discs Large 1, a MAGUK (Membrane Associated Guanylate Kinase) family member that is the highly conserved homolog of mammalian PSD-95 and SAP97. The intol mutation disrupted specifically the expression of DlgS97, a SAP97 homolog, and one of two major protein isoforms encoded by dlg1 via alternative splicing. Expression of the major isoform, DlgA, a PSD-95 homolog, appeared unaffected. Ethanol tolerance in the intol mutant could be partially restored by transgenic expression of DlgS97, but not DlgA, in specific neurons of the fly{\textquoteright}s brain. Based on co-immunoprecipitation, DlgS97 forms a complex with N-methyl-D-aspartate (NMDA) receptors, a known target of ethanol. Consistent with these observations, flies expressing reduced levels of the essential NMDA receptor subunit dNR1 also showed reduced ethanol tolerance, as did mutants in the gene calcium/calmodulin-dependent protein kinase (caki), encoding the fly homolog of mammalian CASK, a known binding partner of DlgS97. Lastly, mice in which SAP97, the mammalian homolog of DlgS97, was conditionally deleted in adults failed to develop rapid tolerance to ethanol{\textquoteright}s sedative/hypnotic effects. We propose that DlgS97/SAP97 plays an important and conserved role in the development of tolerance to ethanol via NMDA receptor-mediated synaptic plasticity.</p>
},
	keywords = {Alleles, Alternative Splicing, Animals, Drosophila melanogaster, Drosophila Proteins, Ethanol, Female, Guanylate Kinase, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Mutation, Neurons, Protein Isoforms, Receptors, N-Methyl-D-Aspartate, Repressor Proteins, Tumor Suppressor Proteins},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0048967},
	author = {Maiya, Rajani and Lee, Seonok and Berger, Karen H and Kong, Eric C and Slawson, Justin B and Griffith, Leslie C and Takamiya, Kogo and Huganir, Richard L and Margolis, Ben and Heberlein, Ulrike}
}
@article {46628,
	title = {GSK-3/Shaggy regulates olfactory habituation in Drosophila.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {104},
	year = {2007},
	month = {2007 Mar 13},
	pages = {4653-7},
	abstract = {<p>Habituation is a universal form of nonassociative learning that results in the devaluation of sensory inputs that have little information content. Although habituation is found throughout nature and has been studied in many organisms, the underlying molecular mechanisms remain poorly understood. We performed a forward genetic screen in Drosophila to search for mutations that modified habituation of an olfactory-mediated locomotor startle response, and we isolated a mutation in the glycogen synthase kinase-3 (GSK-3) homolog Shaggy. Decreases in Shaggy levels blunted habituation, whereas increases promoted habituation. Additionally, habituation acutely regulated Shaggy by an inhibitory phosphorylation mechanism, suggesting that a signal transduction pathway that regulates Shaggy is engaged during habituation. Although shaggy mutations also affected circadian rhythm period, this requirement was genetically separable from its role in habituation. Thus, shaggy functions in different neuronal circuits to regulate behavioral plasticity to an olfactory startle and circadian rhythmicity.</p>
},
	keywords = {Alleles, Animals, Behavior, Animal, Circadian Rhythm, Drosophila, Drosophila Proteins, Female, Glycogen Synthase Kinase 3, Habituation, Psychophysiologic, Male, Models, Genetic, Mutation, Phosphorylation, Signal Transduction, Smell},
	issn = {0027-8424},
	doi = {10.1073/pnas.0700493104},
	author = {Wolf, Fred W and Eddison, Mark and Lee, Seonok and Cho, William and Heberlein, Ulrike}
}
