Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Kristín E. Allison, Morteza Bajgiran, Stefán Eggertsson, Margrét H. Ögmundsdóttir, Zophonías O. Jónsson og Sigríður Rut Franzdóttir
Starfsvettvangur / Affiliations: Háskóli Íslands
Kynnir / Presenter: Sigríður Rut Franzdóttir
Neurons are incredibly long-lived cells which must retain resilience, responsiveness, and plasticity throughout the lifetime of the individual. Many detrimental disorders result from failure in maintenance of neuronal integrity and connections between neurons and their counterparts. Failure to establish or maintain a functional connection between motor neurons and muscles at neuromuscular junctions (NMJs) results in decreased motor activity and muscle atrophy. The maintenance of active proteostasis is key to neuronal resilience and longevity. Production and destruction of proteins must be tightly regulated and misfolded or aggregating peptides rapidly identified and cleared to prevent accumulation in axons and dendrites. The interaction between the translational machinery, the ubiquitin-proteasome (UPS) system and autophagy is essential in this sense, especially under proteolytic stress. We study the specific roles of an ATPase complex in setting up and maintaining healthy motor neurons in Drosophila melanogaster. We have found the complex to be required for constraining synaptic growth during NMJ development, and its loss of function leads to progressive loss of motor skills and the accumulation of ubiquitinated proteins, indicating failure in proteostasis and/or transport. Using genetic tools and advanced imaging, we are further dissecting the roles of the proteins at the intersection of proteostatic processes and at the NMJ.