Endosomal sorting protein SNX4 limits synaptic vesicle docking and release DOI Open Access

Josse Poppinga,

Nolan J. Barret,

L. Niels Cornelisse

et al.

Published: Nov. 26, 2024

Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how affects synapse function remains unknown. We generated a conditional knock-out mouse model and report that cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. depletion did not affect vesicle recycling, basic autophagic flux or levels localization SNARE-protein VAMP2/synaptobrevin-2. However, affected ultrastructure: increase docked synaptic vesicles at active zone, overall number normal, decreased zone length. These effects together lead to substantially increased density per release site. conclusion, negative regulator docking release. findings suggest role for recruitment zone.

Language: Английский

Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors DOI Creative Commons
Michael W. Gongwer, Fanny Etienne,

Eric N. Moca

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract While CNS microglia have well-established roles in synapse pruning during neurodevelopment, only a few studies identified for formation. These focused on the cortex and primary sensory circuits restricted developmental time periods, leaving substantial gaps our understanding of early functions microglia. Here we investigated how absence impacts synaptic development nucleus accumbens (NAc), region critical emotional regulation motivated behaviors where dysfunction is implicated psychiatric disorders that arise life. Using genetically modified mouse lacks ( Csf1r ΔFIRE/ΔFIRE ), found blunted excitatory formation NAc. This effect was most prominent second third postnatal weeks, when previously to be overproduced, accompanied by an increase presynaptic release probability alterations postsynaptic kinetics. Tissue-level NAc proteomics confirmed microglial impacted numerous proteins involved structure, trans-synaptic signaling, pre-synaptic function. However, did not perturb levels astrocyte-derived cues adhesive promote synaptogenesis, suggesting reduced number may caused microglial-derived synaptogenic cue. Although observed electrophysiological changes were largely normalized adulthood, lasting effects threat avoidance behavior, these behavioral directly associated with neuronal activity. Together, results indicate role regulating landscape developing establishing functional underlying adult repertoires.

Language: Английский

Citations

0
Mechanisms by which SNX-BAR subfamily controls the fate of SNXs’ cargo DOI Creative Commons

Yaolin Long,

Li Yang, Xue Jin

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

The SNX-BAR subfamily is a component of the sorting nexins (SNXs) superfamily. Distinct from other SNXs, which feature PX domain for phosphoinositide binding, includes BAR that induces membrane curvature. Members work together to recognize and select specific cargo, regulate receptor signaling, manage cargo both with without involvement complexes. They play crucial role in maintaining cellular homeostasis by directing intracellular appropriate locations through endo-lysosomal, autophagolysosomal, ubiquitin-proteasome pathways. This thus links various protein review examines established hypothesized functions subfamily, its stability, explores potential dysfunction pathophysiology cardiovascular neurodegenerative diseases.

Language: Английский

Citations

0
Vesicular Trafficking in Neuronal Development DOI
Jini Sugatha, Sunando Datta

˜The œReceptors, Journal Year: 2025, Volume and Issue: unknown, P. 399 - 410

Published: Jan. 1, 2025

Language: Английский

Citations

0
Neuronostatin regulates neuronal function and energetic metabolism in Alzheimer's disease in a GPR107-dependent manner DOI
Shaobin Yang, Qi Tang,

Yimeng Zhang

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 258, P. 110090 - 110090

Published: July 22, 2024

Language: Английский

Citations

2
Endosomal sorting protein SNX4 limits synaptic vesicle docking and release DOI Creative Commons

Josse Poppinga,

Nicholas Barrett, L. Niels Cornelisse

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Dec. 19, 2024

Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how affects synapse function remains unknown. We generated a conditional knock-out mouse model and report that cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. depletion did not affect vesicle recycling, basic autophagic flux, or levels localization SNARE-protein VAMP2/synaptobrevin-2. However, affected ultrastructure: increase docked synaptic vesicles at active zone, overall number normal, decreased zone length. These effects together lead to substantially increased density per release site. conclusion, negative regulator docking release. findings suggest role for recruitment zone.

Language: Английский

Citations

1
Endosomal sorting protein SNX4 limits synaptic vesicle docking and release DOI Creative Commons

Josse Poppinga,

Nolan J. Barret,

L. Niels Cornelisse

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 18, 2024

Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how affects synapse function remains unknown. We generated a conditional knock-out mouse model and report that cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. depletion did not affect vesicle recycling, basic autophagic flux or levels localization SNARE-protein VAMP2/synaptobrevin-2. However, affected ultrastructure: increase docked synaptic vesicles at active zone, overall number normal, decreased zone length. These effects together lead to substantially increased density per release site. conclusion, negative regulator docking release. findings suggest role for recruitment zone.

Language: Английский

Citations

0
Endosomal sorting protein SNX4 limits synaptic vesicle docking and release DOI Open Access

Josse Poppinga,

Nolan J. Barret,

L. Niels Cornelisse

et al.

Published: May 7, 2024

Sortin-Nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how affects synapse function remains unknown. We generated a conditional knock-out mouse model and report that cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. depletion did not affect vesicle recycling or levels localization SNARE-protein VAMP2/synaptobrevin-2. However, affected ultrastructure: increase docked synaptic vesicles at active zone, overall number normal, decreased zone length. These effects together lead to substantially increased density per release site. conclusion, negative regulator docking release. findings suggest role for recruitment zone.

Language: Английский

Citations

0
Endosomal sorting protein SNX4 limits synaptic vesicle docking and release DOI Creative Commons

Josse Poppinga,

Nicholas Barrett, L. Niels Cornelisse

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: May 7, 2024

Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how affects synapse function remains unknown. We generated a conditional knock-out mouse model and report that cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. depletion did not affect vesicle recycling, basic autophagic flux, or levels localization SNARE-protein VAMP2/synaptobrevin-2. However, affected ultrastructure: increase docked synaptic vesicles at active zone, overall number normal, decreased zone length. These effects together lead to substantially increased density per release site. conclusion, negative regulator docking release. findings suggest role for recruitment zone.

Language: Английский

Citations

0
The Role of Snx4 in Shaping Immune Infiltration: Implications for Colon Cancer Diagnosis and Prognosis DOI
Yan Zhou, Shilin Lv,

Hongtao Sun

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
SNX32 Regulates Sorting and Trafficking of Activated EGFR to the Lysosomal Degradation Pathway DOI
Dou Wang,

Xia Zhao,

Panpan Wang

et al.

Traffic, Journal Year: 2024, Volume and Issue: 25(7)

Published: July 1, 2024

ABSTRACT SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain‐ and Bin/Amphiphysin/Rvs (BAR) containing sorting nexin (SNX‐BAR) family proteins, which play important roles in membrane trafficking endosomal cargoes. Although shares highest amino acid sequence with SNX6, has been believed to function redundantly SNX5 SNX6 retrieval cation‐independent mannose‐6‐phosphate receptor (CI‐MPR) from endosomes trans ‐Golgi network (TGN), its role(s) intracellular protein remains largely unexplored. Here, we report that it functions parallel SNX1 mediating epidermal growth factor (EGF)‐stimulated postendocytic (EGFR). Moreover, interacts directly EGFR, recruits promote EGF–EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, distinctively other SNX‐BAR proteins mediate signaling‐coupled endolysosomal EGFR.

Language: Английский

Citations

0