The needs of a synapse-How local organelles serve synaptic proteostasis

TY - JOUR

T1 - The needs of a synapse-How local organelles serve synaptic proteostasis

AU - Grochowska, Katarzyna M

AU - Andres-Alonso, Maria

AU - Karpova, Anna

AU - Kreutz, Michael R

N1 - © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

PY - 2022/4/4

Y1 - 2022/4/4

N2 - Synaptic function crucially relies on the constant supply and removal of neuronal membranes. The morphological complexity of neurons poses a significant challenge for neuronal protein transport since the machineries for protein synthesis and degradation are mainly localized in the cell soma. In response to this unique challenge, local micro-secretory systems have evolved that are adapted to the requirements of neuronal membrane protein proteostasis. However, our knowledge of how neuronal proteins are synthesized, trafficked to membranes, and eventually replaced and degraded remains scarce. Here, we review recent insights into membrane trafficking at synaptic sites and into the contribution of local organelles and micro-secretory pathways to synaptic function. We describe the role of endoplasmic reticulum specializations in neurons, Golgi-related organelles, and protein complexes like retromer in the synthesis and trafficking of synaptic transmembrane proteins. We discuss the contribution of autophagy and of proteasome-mediated and endo-lysosomal degradation to presynaptic proteostasis and synaptic function, as well as nondegradative roles of autophagosomes and lysosomes in signaling and synapse remodeling. We conclude that the complexity of neuronal cyto-architecture necessitates long-distance protein transport that combines degradation with signaling functions.

AB - Synaptic function crucially relies on the constant supply and removal of neuronal membranes. The morphological complexity of neurons poses a significant challenge for neuronal protein transport since the machineries for protein synthesis and degradation are mainly localized in the cell soma. In response to this unique challenge, local micro-secretory systems have evolved that are adapted to the requirements of neuronal membrane protein proteostasis. However, our knowledge of how neuronal proteins are synthesized, trafficked to membranes, and eventually replaced and degraded remains scarce. Here, we review recent insights into membrane trafficking at synaptic sites and into the contribution of local organelles and micro-secretory pathways to synaptic function. We describe the role of endoplasmic reticulum specializations in neurons, Golgi-related organelles, and protein complexes like retromer in the synthesis and trafficking of synaptic transmembrane proteins. We discuss the contribution of autophagy and of proteasome-mediated and endo-lysosomal degradation to presynaptic proteostasis and synaptic function, as well as nondegradative roles of autophagosomes and lysosomes in signaling and synapse remodeling. We conclude that the complexity of neuronal cyto-architecture necessitates long-distance protein transport that combines degradation with signaling functions.

U2 - 10.15252/embj.2021110057

DO - 10.15252/embj.2021110057

M3 - SCORING: Review article

C2 - 35285533

VL - 41

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 7

M1 - e110057

ER -