Anastral Spindle 3/Rotatin Stabilizes Sol narae and Promotes Cell Survival in Drosophila melanogaster

• Published in: Molecules and cells 2021, 44(1), , pp.13-26
• Main Authors: Cho, Dong-Gyu, Lee, Sang-Soo, Cho, Kyung-Ok
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Cell Survival; Drosophila melanogaster - cytology; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epistasis, Genetic; Exosomes - metabolism; Gene Knockdown Techniques; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Mutation - genetics; Protein Stability; Wings, Animal - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2020.0244

Apoptosis and compensatory proliferation, two intertwined cellular processes essential for both development and adult homeostasis, are often initiated by the mis-regulation of centrosomal proteins, damaged DNA, and defects in mitosis. Fly Anastral spindle 3 (Ana3) is a member of the pericentriolar matrix proteins and known as a key component of centriolar cohesion and basal body formation. We report here that is a suppressor of lethality induced by the overexpression of Sol narae (Sona), a metalloprotease in a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) family. has a nonsense mutation that truncates the highly conserved carboxyl terminal region containing multiple Armadillo repeats. Lethality induced by Sona overexpression was completely rescued by knockdown of Ana3, and the small and malformed wing and hinge phenotype induced by the knockdown of Ana3 was also normalized by Sona overexpression, establishing a mutually positive genetic interaction between and p35 inhibited apoptosis and rescued the small wing and hinge phenotype induced by knockdown of . Furthermore, overexpression of Ana3 increased the survival rate of irradiated flies and reduced the number of dying cells, demonstrating that Ana3 actively promotes cell survival. Knockdown of Ana3 decreased the levels of both intra- and extracellular Sona in wing discs, while overexpression of Ana3 in S2 cells dramatically increased the levels of both cytoplasmic and exosomal Sona due to the stabilization of Sona in the lysosomal degradation pathway. We propose that one of the main functions of Ana3 is to stabilize Sona for cell survival and proliferation.