Msp300 Links Autophagy to Nuclear Morphodynamics
Autophagy is a fundamental cellular process that maintains homeostasis and enables adaptation to stress by degrading damaged or superfluous components. While its core machinery is well characterized, the interplay between autophagy and nuclear architecture remains poorly understood. In this study, we identify the LINC complex protein Msp300 as a novel interactor of the autophagy protein Atg8a in Drosophila melanogaster. Msp300 belongs to the KASH (Klarsicht/ANC-1/Syne Homology) domain protein family, known for its role in nuclear positioning through interactions with the cytoskeleton. The KASH domain anchors Msp300 in the outer nuclear membrane, where it pairs with SUN domain proteins across the nuclear envelope to form the LINC complex, a mechanical bridge between the nucleoskeleton and cytoskeleton. Yeast two-hybrid screening revealed an interaction between Atg8a and Msp300 isoforms E and G, mediated by a canonical LC3-interacting region (LIR). Localization studies show Msp300 associates with Atg8a within the cytoplasm and at the nuclear periphery under both basal and elevated autophagy conditions. Functional perturbations through stress assays indicate that this interaction influences event in and around nucleus, establishing a link between autophagy and nuclear architecture. By exploring the role of Msp300 isoforms E and G in shaping not only nuclear organization but potentially endoplasmic reticulum, through autophagy machinery, this study introduces a new dimension to nuclear envelope biology and opens opportunities to explore how steady state homeostasis, stress adaptation and cytoskeletal connectivity are coordinated at the nuclear periphery.