Abstract
ABSTRACTMembrane protein turnover and degradation are required for the function and health of all cells. Neurons may live for the entire lifetime of an organism and are highly polarized cells with spatially segregated axonal and dendritic compartments. Both longevity and morphological complexity represent challenges for regulated membrane protein degradation. To investigate how neurons cope with these challenges, an increasing number of recent studies investigated local, cargo‐specific protein sorting, and degradation at axon terminals and in dendritic processes. In this review, we explore the current answers to the ensuing questions of where, what, and when membrane proteins are degraded in neurons. © 2017 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 283–297, 2018
Highlights
Continuous synthesis and degradation through homeostatic regulation of protein turnover ensure a functional pool of proteins
Two neuron-specific proteins that predominantly function at synaptic terminals have been reported to constitute a local, neuronspecific branch of the endolysosomal degradation system: the vesicular ATPase component V100 and the vesicle SNARE neuronal Synaptobrevin (n-Syb) (Williamson et al, 2010a; Haberman et al, 2012; Wang and Hiesinger, 2012; Bezprozvanny and Hiesinger, 2013)
Autophagy is highly conserved from yeast to mammals, and most of our knowledge is derived from studies in non-neuronal cells or neuronal cell bodies (Ohsumi, 2014)
Summary
Continuous synthesis and degradation through homeostatic regulation of protein turnover ensure a functional pool of proteins. Defects in cytosolic and membrane protein degradation typically result in protein accumulation and neuronal dysfunction. Such defects can occur at synapses prior to defects in the cell body and are hallmarks of many neurodegenerative diseases (Arendt, 2009; Shankar and Walsh, 2009; Wong and Cuervo, 2010; Morales et al, 2015; Soto and Kerschensteiner, 2015). Despite the abundance of transmembrane proteins in both presynaptic and postsynaptic compartments, progress has only recently been made to address what membrane proteins are degraded by either mechanism in neurons (Ashrafi and Schwarz, 2013; Huber and Teis, 2016; Mancias and Kimmelman, 2016; Zaffagnini and Martens, 2016; Vijayan and Verstreken, 2017). We will focus on membrane degradation via the autophagosomal and endolysosomal system, and our current understanding of where, what, and when these mechanisms degrade membrane proteins in neurons independent of disease-specific neurotoxic insults
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