Reference Report

Reference
Citation	Ratnaparkhi, A., Lawless, G.M., Schweizer, F.E., Golshani, P., Jackson, G.R. (2008). A Drosophila model of ALS: human ALS-associated mutation in VAP33A suggests a dominant negative mechanism. PLoS ONE 3(6): e2334. (Export to RIS)
FlyBase ID	FBrf0210268
Publication Type	Research paper
PubMed ID	18523548
PubMed Abstract	ALS8 is caused by a dominant mutation in an evolutionarily conserved protein, VAPB (vesicle-associated membrane protein (VAMP)-associated membrane protein B)/ALS8). We have established a fly model of ALS8 using the corresponding mutation in Drosophila VAPB (dVAP33A) and examined the effects of this mutation on VAP function using genetic and morphological analyses. By simultaneously assessing the effects of VAP(wt) and VAP(P58S) on synaptic morphology and structure, we demonstrate that the phenotypes produced by neuronal expression of VAP(P58S) resemble VAP loss of function mutants and are opposite those of VAP overexpression, suggesting that VAP(P58S) may function as a dominant negative. This is brought about by aggregation of VAP(P58S) and recruitment of wild type VAP into these aggregates. Importantly, we also demonstrate that the ALS8 mutation in dVAP33A interferes with BMP signaling pathways at the neuromuscular junction, identifying a new mechanism underlying pathogenesis of ALS8. Furthermore, we show that mutant dVAP33A can serve as a powerful tool to identify genetic modifiers of VAPB. This new fly model of ALS, with its robust pathological phenotypes, should for the first time allow the power of unbiased screens in Drosophila to be applied to study of motor neuron diseases.
DOI	10.1371/journal.pone.0002334
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	PLoS ONE
Title	PLoS ONE
Publication Year	2006-
ISBN/ISSN	1932-6203
Data from Reference
Alleles (15)
	Scer\GAL4^Act.PU Scer\GAL4^elav.PLu Scer\GAL4^G14 Scer\GAL4^how-24B Scer\GAL4^Rapgap1-OK6 Scer\GAL4^repo Scer\GAL4^sca.PU Scer\GAL4^tub.PU tkv^{1ΔGSK.Scer\UAS} Vap-33-1^{P58S.cRa.Scer\UAS.T:Ivir\HA1} Vap-33-1^{P58S.cRa.Scer\UAS} Vap-33-1^Scer\UAS.cRa Vap-33-1^{Scer\UAS.T:Hsap\MYC} Vap-33-1^Δ20 Vap-33-1^Δ166
Constructs (9)
	P{Act-GAL4.U} P{GAL4-elav.L} P{sca-GAL4.U} P{tub-GAL4.U} P{UAS-tkv.1ΔGSK} P{UAS-Vap-33-1.P58S.HA} P{UAS-Vap-33-1.P58S.R} P{UAS-Vap-33-1.R} P{UAS-Vap-33-1.wt.myc}
Genes (12)
	brp Csp dlg1 futsch Mad Scer\GAL4 Syt1 Syx1A T:Hsap\MYC T:Ivir\HA1 tkv Vap-33-1
Insertions (4)
	P{GAL4}G14 P{GAL4}repo P{GawB}how^24B P{GawB}OK6