PKA Activity-Driven Modulation of Bidirectional Long-Distance transport of Lysosomal vesicles During Synapse Maintenance DOI

Kerriann K. Badal,

Yibo Zhao,

Bindu Raveendra

et al.

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

Published: June 30, 2024

Abstract The bidirectional long-distance transport of organelles is crucial for cell body-synapse communication. However, the mechanisms by which this modulated synapse formation, maintenance, and plasticity are not fully understood. Here, we demonstrate through quantitative analyses that maintaining sensory neuron-motor neuron synapses in Aplysia gill-siphon withdrawal reflex linked to a sustained reduction retrograde lysosomal vesicles neurons. Interestingly, while mitochondrial anterograde direction increases within 12 hours vesicle appears three days after formation. Moreover, find formation new during learning induced neuromodulatory neurotransmitter serotonin further reduces 24 hours, whereas one hour exposure. Pharmacological inhibition several signaling pathways pinpoints PKA as key regulator maintenance. These results leads organelle-specific specific enduring changes transport, offering insights into underlying maintenance plasticity.

Language: Английский

Transcriptional and functional profiles of muscarinic receptor-expressing neurons in primate lateral prefrontal and anterior cingulate cortices DOI
Alexandra Tsolias, Chromewell A. Mojica,

Raghad Yamani

et al.

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

Published: May 24, 2025

Acetylcholine modulates anterior cingulate (ACC) and lateral prefrontal (LPFC) cortices for cognitive-motivational integration, via specific m1-m4 muscarinic receptors (mAChR) encoded by CHRM1-4 genes. Single-nucleus RNA sequencing mRNA-protein histology in macaques revealed CHRM3 to be the most enriched mAChR gene neurons, while m1 predominates at protein level, likely due nuclear retention of cytoplasmic trafficking CHRM1. CHRM1 showed strong co-expression functional overlap, were transcriptomically-distinct from CHRM2, which was uniquely deep layer excitatory PVALB + inhibitory neurons. Although CHRM cell distributions similar between areas, CHRM1-3 neurons ACC exhibited upregulation synaptic plasticity genes relative LPFC. Functional vitro experiments confirm a more robust cholinergic-mediated decrease excitatory:inhibitory ratio than LPFC accompanied compensatory changes spine morphology. These findings highlight region-specific acetylcholine signaling essential flexible processing, learning memory.

Language: Английский

Citations

0
Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives DOI Creative Commons
Silvestre Cuinat, Stéphane Bézieau, Wallid Deb

et al.

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(6), P. 101130 - 101130

Published: Sept. 26, 2023

The recent advances in high throughput sequencing technology have drastically changed the practice of medical diagnosis, allowing for rapid identification hundreds genes causing human diseases. This unprecedented progress has made clear that most forms intellectual disability affect more than 3% individuals worldwide are monogenic Strikingly, a substantial fraction mendelian is associated with related to ubiquitin-proteasome system, highly conserved pathway up approximately 1200 involved regulation protein homeostasis. Within this group currently emerging new class neurodevelopmental disorders specifically caused by proteasome pathogenic variants which we propose designate "neurodevelopmental proteasomopathies". Besides cognitive impairment, these diseases typically series syndromic clinical manifestations, among facial dysmorphism, motor delay, and failure thrive prominent ones. While efforts been uncover effects exerted on cell tissue landscapes, molecular pathogenesis proteasomopathies remains ill-defined. In review, discuss cellular changes induced genomic alterations explore their relevance as biomarkers management, potential treatment rare disease entities.

Language: Английский

Citations

5
Synaptic cell adhesion molecules contribute to the pathogenesis and progression of fragile X syndrome DOI Creative Commons

Shu-Yuan Bai,

De-Yang Zeng,

Ming Ouyang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 3, 2024

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and a monogenic cause autism spectrum disorders. Deficiencies in fragile messenger ribonucleoprotein, encoded by FMR1 gene, lead to various anatomical pathophysiological abnormalities behavioral deficits, such as spine dysmorphogenesis learning memory impairments. Synaptic cell adhesion molecules (CAMs) play crucial roles synapse formation neural signal transmission promoting new synaptic contacts, accurately organizing presynaptic postsynaptic protein complexes, ensuring accuracy transmission. Recent studies have implicated CAMs immunoglobulin superfamily, N-cadherin, leucine-rich repeat proteins, neuroligin-1 pathogenesis FXS found that they contribute defects dendritic spines plasticity animal models. This review systematically summarizes biological associations between nine representative FMRP, well functional consequences interaction, provide insights into mechanisms abnormal development FXS.

Language: Английский

Citations

1
PKA Activity-Driven Modulation of Bidirectional Long-Distance transport of Lysosomal vesicles During Synapse Maintenance DOI

Kerriann K. Badal,

Yibo Zhao,

Bindu Raveendra

et al.

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

Published: June 30, 2024

Abstract The bidirectional long-distance transport of organelles is crucial for cell body-synapse communication. However, the mechanisms by which this modulated synapse formation, maintenance, and plasticity are not fully understood. Here, we demonstrate through quantitative analyses that maintaining sensory neuron-motor neuron synapses in Aplysia gill-siphon withdrawal reflex linked to a sustained reduction retrograde lysosomal vesicles neurons. Interestingly, while mitochondrial anterograde direction increases within 12 hours vesicle appears three days after formation. Moreover, find formation new during learning induced neuromodulatory neurotransmitter serotonin further reduces 24 hours, whereas one hour exposure. Pharmacological inhibition several signaling pathways pinpoints PKA as key regulator maintenance. These results leads organelle-specific specific enduring changes transport, offering insights into underlying maintenance plasticity.

Language: Английский

Citations

0