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  • UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila.

UVRAG is required for organ rotation by regulating Notch endocytosis in Drosophila.

Developmental biology (2011-07-07)
Gina Lee, Chengyu Liang, Gihyun Park, Cholsoon Jang, Jae U Jung, Jongkyeong Chung
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-UVRAG antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)