Endophilin-A/SH3GL2 calcium switch for synaptic autophagy induction is impaired by a Parkinson’s risk variant

Decet, Marianna; Soukup, Sandra‐Fausia

doi:10.1080/15548627.2023.2200627

Cited by 8 publications

(6 citation statements)

References 2 publications

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“…related to Parkinson’s, has not been yet connected to via their role on pancreatic cells to the disease. The gene apparently plays a more direct role, acting on brain synapses (Decet & Soukup, 2023). SH3GL2 is reportedly expressed in pancreatic endocrine cells, but we could not find much information about its role in the organ, as most papers seem to focus on its role in the central nervous system.…”

Section: Resultsmentioning

confidence: 99%

Bringing PanglaoDB to 5-star Linked Open Data using Wikidata

Lubiana,

Cavalcante

2024

Preprint

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PanglaoDB is a database of cell-type markers widely used for single-cell RNA sequencing data analysis. However, cell types and genes in the database are encoded by free text, lacking proper identifiers. Wikidata, is a freely editable knowledge graph database useful for integrating biomedical knowledge. We thus reasoned that porting PanglaoDB's markers to the platform could improve their reusability and overall technical quality (FAIRness). We mapped 188 cell types from PanglaoDB to species-neutral terms on Wikidata and created 376 species-specific terms for cell types in Homo sapiens and Mus musculus. These terms were enriched with marker information via the has marker (P8872) property, totaling over 15.000 cell type X marker associations (w.wiki/9iw6). We explored this new subset of the graph via SPARQL queries, illustrating the discovery potential of structured, integrated knowledge. For example, we found a previously unexplored link between rosehip neurons, clozapine, and schizophrenia via the HRH1 marker. Besides the graph-based insights, we took time to describe the details of the reconciliation process, hoping to stimulate more resources for a move to a 5-star linked open data format.

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Section: Resultsmentioning

confidence: 99%

Bringing PanglaoDB to 5-star Linked Open Data using Wikidata

Lubiana,

Cavalcante

2024

Preprint

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“…Thus, our results show that autophagy flux is normal in syngr null mutant synapses, suggesting that lowering the levels of Syngr increases autophagosome biogenesis. As above mentioned, neuronal activity can promote autophagosome biogenesis at the presynaptic compartment 10,12,14,15 . Considering that neuronal activity mobilizes synaptic vesicles and that Syngr is a synaptic vesicle protein, we reasoned that Syngr could regulate neuronal activity-induced autophagy.…”

Section: Synaptogyrin Regulates Synaptic Autophagy In Response To Neu...mentioning

confidence: 87%

“…However, little is still known about how autophagy is regulated in neuronal compartments in response to stimuli besides starvation such as neuronal activity. Indeed, neuronal activity are reported to activate autophagy, leading to autophagosome biogenesis at the synapse 10,[12][13][14][15][16] . Besides their importance, the molecular mechanisms coupling the activation and/or regulation of autophagy in response to these stimuli and to particular cellular processes is still not well understood in neurons and specifically at the synapse 10 .…”

Section: Introductionmentioning

confidence: 99%

Synaptogyrin regulates neuronal activity dependent autophagy to degrade synaptic vesicle components and pathological Tau

Hernandez-Diaz,

Martinez-Olondo,

Sanchez-Mirasierra

et al. 2023

Preprint

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Synapses are specialized neuronal compartments essential for brain communication. Neuronal communication mostly relies on the adequate supply and renovation of synaptic vesicles that fuse with the plasma membrane and release neurotransmitters in response to action potentials. Autophagy is an evolutionary conserved cellular mechanism essential for homeostasis that can be locally regulated in the neuronal synapse. However, the precise mechanisms controlling synaptic autophagy, especially during neuronal communication and pathological scenarios, remain elusive. Here, we report that neuronal activity and amino-acid deprivation regulate synaptic autophagy via distinct molecular mechanisms. We show that Synaptogyrin, a highly abundant presynaptic protein found in synaptic vesicles, is a novel negative regulator of synaptic autophagy in response to neuronal activity without affecting autophagy induction via amino-acid deprivation. We demonstrate that loss of Synaptogyrin modifies the localization of the autophagy protein Atg9 and boosts autophagosome formation at the synapse. Furthermore, activation of synaptic autophagy by loss of Synaptogyrin, but not by amino acid deprivation, leads to the degradation of synaptic vesicle components via autophagy. Reducing the levels of Synaptogyrin results in the degradation of synaptic TAU via autophagy and restores autophagy dysfunction observed in a Drosophila Tau model of Frontotemporal Dementia (FTD). Our data provide novel and valuable information to understand how autophagy is regulated at the synapse in response to neuronal activity and how this process participates in neuronal (dys)function.

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“…Another PD risk mutation in EndoA at the SH3 domain containing GRB2 like 2 (SH3GL2) has been described as disrupting the calcium sensing of SH3GL2. The resultant immobile protein cannot respond to calcium influx and therefore disrupts autophagy induction at the synapses [ 148 ]. A PD mutation in the SCA1 domain of synaptojanin inhibits its phosphatase activity.…”

Section: Compartmentalisation Of Neuronal Autophagymentioning

confidence: 99%

Neuronal Autophagy: Regulations and Implications in Health and Disease

Liénard,

Pintart,

Bomont

2024

Cells

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Autophagy is a major degradative pathway that plays a key role in sustaining cell homeostasis, integrity, and physiological functions. Macroautophagy, which ensures the clearance of cytoplasmic components engulfed in a double-membrane autophagosome that fuses with lysosomes, is orchestrated by a complex cascade of events. Autophagy has a particularly strong impact on the nervous system, and mutations in core components cause numerous neurological diseases. We first review the regulation of autophagy, from autophagosome biogenesis to lysosomal degradation and associated neurodevelopmental/neurodegenerative disorders. We then describe how this process is specifically regulated in the axon and in the somatodendritic compartment and how it is altered in diseases. In particular, we present the neuronal specificities of autophagy, with the spatial control of autophagosome biogenesis, the close relationship of maturation with axonal transport, and the regulation by synaptic activity. Finally, we discuss the physiological functions of autophagy in the nervous system, during development and in adulthood.

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Endophilin-A/SH3GL2 calcium switch for synaptic autophagy induction is impaired by a Parkinson’s risk variant

Cited by 8 publications

References 2 publications

Bringing PanglaoDB to 5-star Linked Open Data using Wikidata

Bringing PanglaoDB to 5-star Linked Open Data using Wikidata

Synaptogyrin regulates neuronal activity dependent autophagy to degrade synaptic vesicle components and pathological Tau

Neuronal Autophagy: Regulations and Implications in Health and Disease

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