Recent insights on principles of synaptic protein degradation

F1000Res. 2017 May 15;6:675. doi: 10.12688/f1000research.10599.1. eCollection 2017.

Abstract

Maintaining synaptic integrity and function depends on the continuous removal and degradation of aged or damaged proteins. Synaptic protein degradation has received considerable attention in the context of synaptic plasticity and growing interest in relation to neurodegenerative and other disorders. Conversely, less attention has been given to constitutive, ongoing synaptic protein degradation and the roles canonical degradation pathways play in these processes. Here we briefly review recent progress on this topic and new experimental approaches which have expedited such progress and highlight several emerging principles. These include the realization that synaptic proteins typically have unusually long lifetimes, as might be expected from the remote locations of most synaptic sites; the possibility that degradation pathways can change with time from synthesis, cellular context, and physiological input; and that degradation pathways, other than ubiquitin-proteasomal-mediated degradation, might play key roles in constitutive protein degradation at synaptic sites. Finally, we point to the importance of careful experimental design and sufficiently sensitive techniques for studying synaptic protein degradation, which bring into account their slow turnover rates and complex life cycles.

Keywords: PKCλ; PKMζ; TS:YFP; autophagy; canonical degradation pathways; synaptic protein degradation; ubiquitin-proteasome system.

Publication types

  • Review

Grant support

We are grateful for the generous funding provided by the DFG German-Israeli Foundation DIP (RO3971/1-1), the Israel Science Foundation (ISF) (1175/14), the Allen and Jewel Prince Center for Neurodegenerative Processes of the Brain, the Rappaport Institute, and the Technion, which made the writing of this review possible.