Neurodegenerative and Neurodevelopmental Roles for Bulk Lipid Transporters VPS13A and BLTP2 DOI Creative Commons
Sarah D. Neuman, Rajan Thakur, Scott J. Gratz

и другие.

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Abstract Background Bridge‐like lipid transfer proteins (BLTPs) mediate bulk transport at membrane contact sites. Mutations in BLTPs are linked to both early‐onset neurodevelopmental and later‐onset neurodegenerative diseases, including movement disorders. The tissue specificity temporal requirements of disease pathogenesis remain poorly understood. Objective objective this study was determine tissue‐specific aging‐dependent roles for VPS13A BLTP2 using Drosophila models. Methods We generated knockdowns the ortholog ( Vps13 ) hobbit neurons muscles . analyzed age‐dependent locomotor behavior, neurodegeneration, synapse development function. Results Neuron‐specific loss caused neurodegeneration followed by deficits reduced lifespan, whereas muscle‐specific affected only lifespan. In contrast, neuronal resulted severe defects without muscle impaired synaptogenesis neurotransmission neuromuscular junction. Conclusions maintains survival, orchestrates synaptic development. phenotypic BLTP function provides mechanistic insights into distinct trajectories BLTP‐associated © 2025 Author(s). Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Язык: Английский

Distinct input-specific mechanisms enable presynaptic homeostatic plasticity DOI Creative Commons
Chun Chien, Kaikai He, Sarah Perry

и другие.

Science Advances, Год журнала: 2025, Номер 11(7)

Опубликована: Фев. 14, 2025

Synapses are endowed with the flexibility to change through experience, but must be sufficiently stable last a lifetime. This tension is illustrated at Drosophila neuromuscular junction (NMJ), where two motor inputs that differ in structural and functional properties coinnervate most muscles coordinate locomotion. To stabilize NMJ activity, neurons augment neurotransmitter release following diminished postsynaptic glutamate receptor functionality, termed presynaptic homeostatic potentiation (PHP). How these distinct contribute PHP plasticity remains enigmatic. We have used botulinum neurotoxin selectively silence each input resolve their roles PHP, demonstrating specific: Chronic (genetic) targets tonic MN-Ib, active zone remodeling enhances Ca 2+ influx promote increased release. In contrast, acute (pharmacological) increases vesicle pools potentiate phasic MN-Is. Thus, modulations nanoarchitecture, pools, collaborate enable input-specific expression.

Язык: Английский

Процитировано

1
Specific presynaptic functions require distinct Drosophila Cav2 splice isoforms DOI Open Access
Christopher J. Bell, Lukas Kilo,

Daniel Gottschalk

и другие.

Опубликована: Янв. 6, 2025

The multiplicity of neural circuits that accommodate the sheer infinite number computations conducted by brains requires diverse synapse and neuron types. At many vertebrate synapses release probability other aspects presynaptic function are tuned different combinations Ca v 2.1, 2.2, 2.3 channels. By contrast, most invertebrate genomes contain only one 2 gene. Drosophila homolog, cacophony (cac), localizes to active zones (AZs) induce synaptic vesicle release. We hypothesize cac functional diversity is enhanced two specific exon pairs mutually exclusively spliced not conserved in vertebrates, voltage sensor intracellular loop containing binding site(s) for β G-protein βγ subunits. test our hypothesis combining opto– electrophysiological with neuroanatomical approaches at a fast glutamatergic model synapse, larval neuromuscular junction. find alternative splicing affects channel activation imperative normal function. Only isoform higher AZ mediates evoked Removal these splice isoforms renders non-functional. encodes between first second homologous repeats does affect localization, but it tunes multiple While expression yields transmission, reduces thus probability. This also abolishes homeostatic plasticity. Moreover, reduced upon selective excision increases paired pulse ratios variability depression during low frequency stimulation trains (1 10 Hz), short term Effects on plasticity can be rescued increasing external calcium concentration match control. In sum, provides mechanism regulate functions

Язык: Английский

Процитировано

0
Building and modifying diverse synaptic properties: Insights from Drosophila DOI
Kaikai He, Dion Dickman

Current Opinion in Neurobiology, Год журнала: 2025, Номер 92, С. 102995 - 102995

Опубликована: Март 9, 2025

Язык: Английский

Процитировано

0
Neurodegenerative and Neurodevelopmental Roles for Bulk Lipid Transporters VPS13A and BLTP2 DOI Creative Commons
Sarah D. Neuman, Rajan Thakur, Scott J. Gratz

и другие.

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Abstract Background Bridge‐like lipid transfer proteins (BLTPs) mediate bulk transport at membrane contact sites. Mutations in BLTPs are linked to both early‐onset neurodevelopmental and later‐onset neurodegenerative diseases, including movement disorders. The tissue specificity temporal requirements of disease pathogenesis remain poorly understood. Objective objective this study was determine tissue‐specific aging‐dependent roles for VPS13A BLTP2 using Drosophila models. Methods We generated knockdowns the ortholog ( Vps13 ) hobbit neurons muscles . analyzed age‐dependent locomotor behavior, neurodegeneration, synapse development function. Results Neuron‐specific loss caused neurodegeneration followed by deficits reduced lifespan, whereas muscle‐specific affected only lifespan. In contrast, neuronal resulted severe defects without muscle impaired synaptogenesis neurotransmission neuromuscular junction. Conclusions maintains survival, orchestrates synaptic development. phenotypic BLTP function provides mechanistic insights into distinct trajectories BLTP‐associated © 2025 Author(s). Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Язык: Английский

Процитировано

0