Chemical synaptic transmission involves neurotransmitter release from presynaptic active zones (AZs). The AZ protein Rab-3-interacting molecule (RIM) is important for normal Ca-triggered release. However, its precise localization within AZs of the glutamatergic neuromuscular junctions of remains elusive. We used CRISPR/Cas9-assisted genome engineering of the locus to incorporate small epitope tags for targeted super-resolution imaging. A V5-tag, derived from simian virus 5, and an HA-tag, derived from human influenza virus, were N-terminally fused to the RIM Zinc finger. Whereas both variants are expressed in co-localization with the core AZ scaffold Bruchpilot, electrophysiological characterization reveals that AP-evoked synaptic release is disturbed in rim but not in rim In addition, rim synapses show intact presynaptic homeostatic potentiation. Combining super-resolution localization microscopy and hierarchical clustering, we detect ∼10 RIM subclusters with ∼13 nm diameter per AZ that are compacted and increased in numbers in presynaptic homeostatic potentiation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494931 | PMC |
| http://dx.doi.org/10.26508/lsa.202302021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA.
Background: The lateral entorhinal cortex (LEC), followed by area CA1 of hippocampus, are interconnected brain areas implicated early in Alzheimer's disease (AD). Processing of LEC input by CA1 pyramidal neurons (PNs) is critical for non-spatial memory, in which deficits are seen in early AD. How this process is affected by tauopathy is unclear.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Tau aggregation is the major cause of several neurodegenerative tauopathies. Tau interaction with other proteins affects the formation of tau aggregates with seeding activity but less is known about its effects on tau-seed properties. Our previous study revealed that Bassoon (BSN), a presynaptic protein, interacts with tau-seed, exacerbating its toxicity in vivo.
View Article and Find Full Text PDFBlobby is a synaptic active zone assembly protein required for memory in Drosophila.
Nat Commun
January 2025
Freie Universität Berlin, Institute for Biology and Genetics, Berlin, Germany.
At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional Drosophila AZ protein, "Blobby", essential for proper AZ nano-organization.
View Article and Find Full Text PDFCardiac Presynaptic Sympathetic Nervous Function Evaluated by Cardiac PET in Patients with Chronotropic Incompetence Without Heart Failure.
J Nucl Med
January 2025
Department of Cardiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Chronotropic incompetence (CTI), the inability of the heart to increase its rate with increased activity, leads to exercise intolerance and predicts overall mortality. We previously reported that cardiac β-adrenergic receptor downregulation occurs in patients with CTI without heart failure (HF), indicating postsynaptic sympathetic nervous dysfunction. However, cardiac presynaptic sympathetic nervous system function in CTI is not fully understood.
View Article and Find Full Text PDFMinimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release.
Nat Commun
December 2024
Nanobiology Institute, Yale University, West Haven, CT, USA.
Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!