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The cleft is an integral part of synapses, yet its macromolecular organization remains unclear. We show here that the cleft of excitatory synapses exhibits a distinct density profile as measured by cryoelectron tomography (cryo-ET). Aiming for molecular insights, we analyzed the synapse-organizing proteins Synaptic Cell Adhesion Molecule 1 (SynCAM 1) and EphB2. Cryo-ET of SynCAM 1 knockout and overexpressor synapses showed that this immunoglobulin protein shapes the cleft's edge. SynCAM 1 delineates the postsynaptic perimeter as determined by immunoelectron microscopy and super-resolution imaging. In contrast, the EphB2 receptor tyrosine kinase is enriched deeper within the postsynaptic area. Unexpectedly, SynCAM 1 can form ensembles proximal to postsynaptic densities, and synapses containing these ensembles were larger. Postsynaptic SynCAM 1 surface puncta were not static but became enlarged after a long-term depression paradigm. These results support that the synaptic cleft is organized on a nanoscale into sub-compartments marked by distinct trans-synaptic complexes.
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http://dx.doi.org/10.1016/j.neuron.2015.11.011 | DOI Listing |
Mol Psychiatry
September 2025
Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Waehringer Strasse 13A, 1090, Vienna, Austria.
The human monoamine transporters (MATs) for serotonin (SERT), dopamine (DAT), and norepinephrine (NET) play a key role in neurotransmission by transporting neurotransmitters from the synaptic cleft back into the neuron. MATs are embedded in the cell membrane's lipid bilayer, encompassing cholesterol, phospholipids, and sphingolipids as main components. Membrane cholesterol association has been shown for all MATs impacting transporter conformation, substrate affinity, transport velocity, and turnover rates.
View Article and Find Full Text PDFExp Eye Res
August 2025
Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politecnico Nacional, Av. IPN 2508, San Pedro Zacatenco, CDMX, 07360, Mexico. Electronic address:
Signal transmission in the visual pathway is carried by glutamate, the major excitatory neurotransmitter in the vertebrate brain. Ionotropic and metabotropic receptors mediate the actions of this amino acid. A tight regulation of extra-synaptic glutamate concentrations is needed for the selective activation of its receptors as a function of the day/night cycle.
View Article and Find Full Text PDFJ Child Neurol
August 2025
Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan.
Synaptic vesicle fusion is a process that involves the release of neurotransmitters from synaptic vesicles into the synaptic cleft. is a protein that mediates synaptic vesicle fusion by forming a complex with other proteins on the presynaptic membrane. Mutations in have been recently identified as a cause of a rare form of hereditary spastic paraplegia (HSP), a group of genetic disorders characterized by the gradual development of muscle stiffness and weakness in the lower extremities.
View Article and Find Full Text PDFJ Physiol
August 2025
School of Biosciences, University of Sheffield, Sheffield, UK.
Head movements are detected and signalled to primary sensory neurons by vestibular types I and II hair cells. Signal transmission involves glutamate exocytosis from hair cells, which is triggered by Ca inflow through voltage-gated Ca1.3 Ca channels.
View Article and Find Full Text PDFNeuroreport
August 2025
Department of Rehabilitation Medicine, College of Medicine, Lishui University, Lishui.
Background: Recent evidence suggests that neuroinflammation and synaptic dysfunction play crucial roles in linking obesity to the development of depression. Long-term consumption of a high-fat (HF) diet not only leads to metabolic disruptions in the body but also disturbs brain homeostasis, particularly affecting the amygdala, a key region involved in regulating depression.
Methods: This study explored the therapeutic potential of geniposide, a bioactive iridoid glycoside known for its antiinflammatory properties, in mitigating HF diet-induced depressive behaviors and amygdala pathology.