ESCRT disruption provides evidence against signaling functions for synaptic exosomes DOI Creative Commons
Erica C. Dresselhaus, Kathryn P. Harris, Cassandra R. Blanchette

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 24, 2023

Extracellular vesicles (EVs) are released by many cell types including neurons, carrying cargoes involved in signaling and disease. It is unclear whether EVs promote intercellular or serve primarily to dispose of unwanted materials. We show that loss multivesicular endosome-generating ESCRT (endosomal sorting complex required for transport) machinery disrupts release EV from Drosophila motor neurons. Surprisingly, depletion does not affect the activities cargo Synaptotagmin-4 (Syt4) only some Evenness Interrupted (Evi). Thus, these may require transfer via EVs, instead be conventionally secreted function autonomously neuron. find phagocytosed glia muscles, disruption causes compensatory autophagy presynaptic suggesting one several redundant mechanisms remove synapses. Our results suggest synaptic serves as a proteostatic mechanism certain cargoes.

Language: Английский

Neuronal activity promotes secretory autophagy for the extracellular release of α-synuclein DOI Creative Commons
Yoshitsugu Nakamura,

Taiki Sawai,

Kensuke Kakiuchi

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(7), P. 107419 - 107419

Published: May 28, 2024

Language: Английский

Citations

10
Canonical and noncanonical autophagy: involvement in Parkinson’s disease DOI Creative Commons
Maria Sakurai, Tomoki Kuwahara

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 30, 2025

Autophagy is the major degradation process in cells and involved a variety of physiological pathological functions. While macroautophagy, which employs series molecular cascades to form ATG8-coated double membrane autophagosomes for degradation, remains well-known type canonical autophagy, microautophagy chaperon-mediated autophagy have also been characterized. On other hand, recent studies focused on functions proteins beyond intracellular including noncanonical known as conjugation ATG8 single membranes (CASM), autophagy-related extracellular secretion. In particular, CASM unique that it does not require upstream mechanisms, while system manner different from autophagy. There many reports involvement these mechanisms neurodegenerative diseases, with Parkinson’s disease (PD) receiving particular attention because important roles several causative risk genes, LRRK2. this review, we will summarize discuss contributions cellular functions, special focus pathogenesis PD.

Language: Английский

Citations

1
Peripheral glia and neurons jointly regulate activity-induced synaptic remodeling at the Drosophila neuromuscular junction DOI Open Access
Yen-Ching Chang, Yi-Jheng Peng, Joo Yeun Lee

et al.

Published: Jan. 6, 2025

In the nervous system, reliable communication depends on ability of neurons to adaptively remodel their synaptic structure and function in response changes neuronal activity. While are main drivers plasticity, glial cells increasingly recognized for roles as active modulators. However, underlying molecular mechanisms remain unclear. Here, using Drosophila neuromuscular junction a model system tripartite synapse, we show that peripheral collaborate with at NMJ regulate activity-induced remodeling, part through protein called shriveled (Shv). Shv is an activator integrin signaling previously shown be released by during intense stimulation fly remodeling. We demonstrate also present glia, both necessary sufficient unlike Shv, does not activate NMJ. Instead, it regulates plasticity two ways: 1) maintaining extracellular balance proteins signaling, 2) controlling ambient glutamate concentration postsynaptic receptor abundance. Loss showed same phenotype loss glia. Together, these results reveal homeostatically levels control Additionally, glia maintains abundance contribute remodeling regulating

Language: Английский

Citations

0
Peripheral glia and neurons jointly regulate activity-induced synaptic remodeling at the Drosophila neuromuscular junction DOI Open Access
Yen-Ching Chang, Yi-Jheng Peng, Joo Yeun Lee

et al.

Published: Jan. 6, 2025

In the nervous system, reliable communication depends on ability of neurons to adaptively remodel their synaptic structure and function in response changes neuronal activity. While are main drivers plasticity, glial cells increasingly recognized for roles as active modulators. However, underlying molecular mechanisms remain unclear. Here, using Drosophila neuromuscular junction a model system tripartite synapse, we show that peripheral collaborate with at NMJ regulate activity-induced remodeling, part through protein called shriveled (Shv). Shv is an activator integrin signaling previously shown be released by during intense stimulation fly remodeling. We demonstrate also present glia, both necessary sufficient unlike Shv, does not activate NMJ. Instead, it regulates plasticity two ways: 1) maintaining extracellular balance proteins signaling, 2) controlling ambient glutamate concentration postsynaptic receptor abundance. Loss showed same phenotype loss glia. Together, these results reveal homeostatically levels control Additionally, glia maintains abundance contribute remodeling regulating

Language: Английский

Citations

0
Neuronal autophagy in the control of synapse function DOI Creative Commons
Anna Karpova, P. Robin Hiesinger, Marijn Kuijpers

et al.

Neuron, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Neurons are long-lived postmitotic cells that capitalize on autophagy to remove toxic or defective proteins and organelles maintain neurotransmission the integrity of their functional proteome. Mutations in genes cause congenital diseases, sharing prominent brain dysfunctions including epilepsy, intellectual disability, neurodegeneration. Ablation core neurons glia disrupts normal behavior, leading motor deficits, memory impairment, altered sociability, which associated with defects synapse maturation, plasticity, neurotransmitter release. In spite importance for physiology, substrates neuronal mechanisms by affect synaptic function health disease remain controversial. Here, we summarize current state knowledge autophagy, address existing controversies inconsistencies field, provide a roadmap future research role control function.

Language: Английский

Citations

0
Lysosomes’ fallback strategies: more than just survival or death DOI Creative Commons
Quan Wang, Ruolin Wang, Hanqing Hu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 11, 2025

Lysosomes are heterogeneous, acidic organelles whose proper functionality is critically dependent on maintaining the integrity of their membranes and acidity within lumen. When subjected to stress, lysosomal membrane can become permeabilized, posing a significant risk organelle’s survival necessitating prompt repair. Although numerous mechanisms for repair have been identified in recent years, progression lysosome-related diseases more closely linked alternative strategies when fail, particularly contexts aging pathogen infection. This review explores responses damage, including secretion contents interactions with lysosome-associated endolysosomal system. Furthermore, it examines role outside this system, such as endoplasmic reticulum (ER) Golgi apparatus, auxiliary These crucial understanding disease progression. For instance, spread misfolded proteins play key roles neurodegenerative advancement, while escape via lysosomotropic drug expulsion underlie cancer treatment resistance. Reexamining these fallback could provide new perspectives biology contribution

Language: Английский

Citations

0
How does autophagy impact neurological function? DOI Creative Commons
Angeleen Fleming, Ana López,

Matea Rob

et al.

The Neuroscientist, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Autophagies describe a set of processes in which cells degrade their cytoplasmic contents via various routes that terminate with the lysosome. In macroautophagy (the focus this review, henceforth autophagy), contents, including misfolded proteins, protein complexes, dysfunctional organelles, and pathogens, are captured within double membranes called autophagosomes, ultimately fuse lysosomes, after degraded. Autophagy is important maintaining neuronal glial function; consequently, disrupted autophagy associated neurologic diseases. This review provides broad perspective on roles CNS, highlighting recent literature furthers our understanding multifaceted role healthy nervous system.

Language: Английский

Citations

0
The life and times of brain autophagic vesicles DOI
Lisa Gambarotto, Erin Wosnitzka, Vassiliki Nikoletopoulou

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169105 - 169105

Published: March 1, 2025

Language: Английский

Citations

0
Autophagy in alzheimer disease pathogenesis and its therapeutic values DOI Creative Commons

Gabrielle Angst,

Nuo Jia,

Luis E. Tron Esqueda

et al.

Autophagy Reports, Journal Year: 2025, Volume and Issue: 4(1)

Published: May 8, 2025

Language: Английский

Citations

0
ESCRT disruption provides evidence against trans-synaptic signaling via extracellular vesicles DOI Creative Commons
Erica C. Dresselhaus, Kathryn P. Harris, Cassandra R. Blanchette

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(9)

Published: June 6, 2024

Extracellular vesicles (EVs) are released by many cell types, including neurons, carrying cargoes involved in signaling and disease. It is unclear whether EVs promote intercellular or serve primarily to dispose of unwanted materials. We show that loss multivesicular endosome-generating endosomal sorting complex required for transport (ESCRT) machinery disrupts release EV from Drosophila motor neurons. Surprisingly, ESCRT depletion does not affect the activities cargo Synaptotagmin-4 (Syt4) only some evenness interrupted (Evi). Thus, these may require transfer via EVs, instead be conventionally secreted function cell-autonomously neuron. find phagocytosed glia muscles, disruption causes compensatory autophagy presynaptic suggesting one several redundant mechanisms remove synapses. Our results suggest synaptic serves as a proteostatic mechanism certain cargoes.

Language: Английский

Citations

3