Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Rannveig Kristjánsdóttir, Morteza Bajgiran, Margrét H. Ögmundsdóttir, Zophonías O. Jónsson, Sigríður Rut Franzdóttir
Starfsvettvangur / Affiliations: Háskóli Íslands
Kynnir / Presenter: Rannveig Kristjánsdóttir
Linking autophagy and aggregate clearance in motor neurons Rannveig Kristjánsdóttir, Morteza Bajgiran, Margrét H. Ögmundsdóttir, Zophonías O. Jónsson, Sigríður Rut Franzdóttir Neuronal dysfunction can arise from the build up of aggregated, intrinsically-disordered or misfolded proteins that cannot be properly degraded. The degradation capacity of neurons is determined by the ubiquitin-proteasome system (UPS) and autophagy. When this capacity is exceeded, cell gather these materials into an aggresome, which subsequently promotes their autophagic clearance. Depletion of the conserved ATPases, Pontin and Reptin impairs the formation of aggresomes in cell culture. The proteins also interact with components of the autophagic machinery and the UPS system. In Drosophila melanogaster, aggregate-like swellings in neurons and neurological dysfunction were observed upon loss of Pontin and Reptin. The distribution of polyubiquitinated peptides indicates impaired aggresome formation and clearance. This may indicate effects on autophagy, transport, and/or impaired recognition of aggregating material. In this project, we investigate the requirement of these two proteins for neuronal autophagy and aggrephagy in motor neurons of the Drosphila melanogaster nervous system. To this end, we knock down pontin and reptin expression specifically in motor neurons, co-expressing fluorescent Atg8 protein as a marker of autophagy, and determine the effect on autophagic vesicle number and subcellula