Autophagy and the endolysosomal system in presynaptic function
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Autophagy and the endolysosomal system in presynaptic function. / Andres-Alonso, Maria; Kreutz, Michael R; Karpova, Anna.
In: CELL MOL LIFE SCI, Vol. 78, No. 6, 11.03.2021, p. 2621-2639.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Autophagy and the endolysosomal system in presynaptic function
AU - Andres-Alonso, Maria
AU - Kreutz, Michael R
AU - Karpova, Anna
PY - 2021/3/11
Y1 - 2021/3/11
N2 - The complex morphology of neurons, the specific requirements of synaptic neurotransmission and the accompanying metabolic demands create a unique challenge for proteostasis. The main machineries for neuronal protein synthesis and degradation are localized in the soma, while synaptic junctions are found at vast distances from the cell body. Sophisticated mechanisms must, therefore, ensure efficient delivery of newly synthesized proteins and removal of faulty proteins. These requirements are exacerbated at presynaptic sites, where the demands for protein turnover are especially high due to synaptic vesicle release and recycling that induces protein damage in an intricate molecular machinery, and where replacement of material is hampered by the extreme length of the axon. In this review, we will discuss the contribution of the two major pathways in place, autophagy and the endolysosomal system, to presynaptic protein turnover and presynaptic function. Although clearly different in their biogenesis, both pathways are characterized by cargo collection and transport into distinct membrane-bound organelles that eventually fuse with lysosomes for cargo degradation. We summarize the available evidence with regard to their degradative function, their regulation by presynaptic machinery and the cargo for each pathway. Finally, we will discuss the interplay of both pathways in neurons and very recent findings that suggest non-canonical functions of degradative organelles in synaptic signalling and plasticity.
AB - The complex morphology of neurons, the specific requirements of synaptic neurotransmission and the accompanying metabolic demands create a unique challenge for proteostasis. The main machineries for neuronal protein synthesis and degradation are localized in the soma, while synaptic junctions are found at vast distances from the cell body. Sophisticated mechanisms must, therefore, ensure efficient delivery of newly synthesized proteins and removal of faulty proteins. These requirements are exacerbated at presynaptic sites, where the demands for protein turnover are especially high due to synaptic vesicle release and recycling that induces protein damage in an intricate molecular machinery, and where replacement of material is hampered by the extreme length of the axon. In this review, we will discuss the contribution of the two major pathways in place, autophagy and the endolysosomal system, to presynaptic protein turnover and presynaptic function. Although clearly different in their biogenesis, both pathways are characterized by cargo collection and transport into distinct membrane-bound organelles that eventually fuse with lysosomes for cargo degradation. We summarize the available evidence with regard to their degradative function, their regulation by presynaptic machinery and the cargo for each pathway. Finally, we will discuss the interplay of both pathways in neurons and very recent findings that suggest non-canonical functions of degradative organelles in synaptic signalling and plasticity.
U2 - 10.1007/s00018-020-03722-5
DO - 10.1007/s00018-020-03722-5
M3 - SCORING: Review article
C2 - 33340068
VL - 78
SP - 2621
EP - 2639
JO - CELL MOL LIFE SCI
JF - CELL MOL LIFE SCI
SN - 1420-682X
IS - 6
ER -