Reference Report

Reference
Citation	Lee, G., Liang, C., Park, G., Jang, C., Jung, J.U., Chung, J. (2011). UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila. Dev. Biol. 356(2): 588--597. (Export to RIS)
FlyBase ID	FBrf0214470
Publication Type	Research paper
PubMed ID	21729695
PubMed Abstract	Heterotaxy characterized by abnormal left-right body asymmetry causes diverse congenital anomalies. Organ rotation is a crucial developmental process to establish the left-right patterning during animal development. However, the molecular basis of how organ rotation is regulated is poorly understood. Here we report that Drosophila UV-resistance associated gene (UVRAG), a tumor suppressor that regulates autophagy and endocytosis, plays unexpected roles in controlling organ rotation. Loss-of-function mutants of UVRAG show seriously impaired organ rotation phenotypes, which are associated with defects in endocytic trafficking rather than autophagy. Blunted endocytic degradation by UVRAG deficiency causes endosomal accumulation of Notch, resulting in abnormally enhanced Notch activity. Knockdown of Notch itself or expression of a dominant negative form of Notch transcriptional co-activator Mastermind is sufficient to rescue the rotation defect in UVRAG mutants. Consistently, UVRAG-mutated heterotaxy patient cells also display highly increased Notch protein levels. These results suggest evolutionarily conserved roles of UVRAG in organ rotation by regulating Notch endocytic degradation.
DOI	10.1016/j.ydbio.2011.06.024
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	Dev. Biol.
Title	Developmental Biology
Publication Year	1959-
ISBN/ISSN	0012-1606
Data from Reference
Aberrations (1)
	Df(2L)ED784
Alleles (28)
	Atg5^{dsRNA.Scer\UAS} Atg7^d14 Atg7^d77 Atg8a^{Scer\UAS.P\T.T:Avic\GFP-EGFP} Atg8a^{Scer\UAS.T:Disc\RFP-mCherry} Dl::N^{ΔECN.Scer\UAS} Egfr^GD1654 mam^N.Scer\UAS N^{dsRNA.P.Scer\UAS} N^ECN.Scer\UAS N^Scer\UAS.cSb ptc^NIG.2411R Pvr^{dsRNA.Scer\UAS.cRa} Rab5^GD10492 Scer\GAL4^Abd-B-LDN Scer\GAL4^da.G32 Scer\GAL4^elav.PU Scer\GAL4^fat Scer\GAL4^hh-Gal4 Scer\GAL4^hs.PU Scer\GAL4^Lsp2.PH Uvrag^B7 Uvrag^B21 Uvrag^GS17330 Uvrag^KG04163 Uvrag^NIG.6116R Uvrag^{Scer\UAS.T:Zzzz\FLAG} Vps25^GD8432
Constructs (19)
	P{elav-GAL4.U} P{GAL4-da.G32} P{GD1654} P{GD8432} P{GD10492} P{hs-GAL4.U} P{Lsp2-GAL4.H} P{NIG.2411R} P{NIG.6116R} P{UAS-Atg5.IR} P{UAS-Dl::N.ΔECN} P{UAS-mamN} P{UAS-mCherry-Atg8a} P{UAS-N.dsRNA.P} P{UAS-N.ECN} P{UAS-N⁺.Sb} P{UASp-Atg8a.EGFP} P{UAS-Pvr.dsRNA.R} P{UAS-Uvrag.Flag}
Genes (15)
	Atg5 Atg7 Atg8a Dl::N Egfr Hrs mam N ptc Pvr Rab5 Scer\GAL4 T:Zzzz\FLAG Uvrag Vps25
Insertions (5)
	P{GAL4}fat P{GAL4}hh^Gal4 P{GawB}Abd-B^LDN P{GSV6}Uvrag^GS17330 P{SUPor-P}Uvrag^KG04163
Natural transposons (1)
	P-element