Project Details
Projekt
Presynaptic crosstalk of autophagy and proteasomal activity to maintain proteostasis
Subject Area
Molecular and Cellular Neurology and Neuropathology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 447288260
Misfolded and damaged proteins that tend to accumulate with ageing need to be removed inorder to maintain cellular function throughout life. This is of particular importance in postmitotic cells such as neurons. The two major proteolytic machines are macroautophagy (referred hereafter as autophagy) and the ubiquitin proteasome system (UPS). Our preliminarywork and the work of others suggests crosstalk and/or compensatory mechanisms betweenthe two systems, which may function in a highly localized fashion to eliminate proteins at thepresynaptic terminals. However, if and how the two systems cooperate, and whether theychange during ageing in an increasingly oxidative environment is not understood and will beexplored in this collaborative research proposal by the Kirstein and Eickholt labs. We aim tostudy the principal capacities of both proteolytic pathways at the presynapse and toinvestigate effector systems that mediate a crosstalk between autophagy and the UPS. Wefurther aim to identify novel presynaptic autophagy substrates using a strategy involving anengineered chaperone system.
DFG Programme
Research Units
