Synaptic vesicles (SVs) store and transport neurotransmitters to the presynaptic active zone for release by exocytosis. After release, SV proteins and excess membrane are recycled via endocytosis, and new SVs can be formed in a clathrin-dependent manner. This process maintains complex molecular composition of SVs through multiple recycling rounds.
View Article and Find Full Text PDFCholesterol is crucial for neuronal synaptic transmission, assisting in the molecular and structural organization of lipid rafts, ion channels, and exocytic proteins. Although cholesterol absence was shown to result in impaired neurotransmission, how cholesterol locally traffics and its route of action are still under debate. Here, we characterized the lipid transfer protein ORP2 in murine hippocampal neurons.
View Article and Find Full Text PDFInner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other.
View Article and Find Full Text PDFEndophilins-A are conserved endocytic adaptors with membrane curvature-sensing and -inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 and endophilin-A2 regulate exocytosis of neurosecretory vesicles. The number and distribution of neurosecretory vesicles were not changed in chromaffin cells lacking endophilin-A, yet fast capacitance and amperometry measurements revealed reduced exocytosis, smaller vesicle pools and altered fusion kinetics.
View Article and Find Full Text PDFHigh-throughput neurotransmission at ribbon synapses of cochlear inner hair cells (IHCs) requires tight coupling of neurotransmitter release and balanced recycling of synaptic vesicles (SVs) as well as rapid restoration of release sites. Here, we examined the role of the adaptor protein AP180 (also known as SNAP91) for IHC synaptic transmission by comparing AP180-knockout (KO) and wild-type mice using high-pressure freezing and electron tomography, confocal microscopy, patch-clamp membrane capacitance measurements and systems physiology. AP180 was found predominantly at the synaptic pole of IHCs.
View Article and Find Full Text PDFRibbon synapses of cochlear inner hair cells (IHCs) operate with high rates of neurotransmission; yet, the molecular regulation of synaptic vesicle (SV) recycling at these synapses remains poorly understood. Here, we studied the role of endophilins-A1-3, endocytic adaptors with curvature-sensing and curvature-generating properties, in mouse IHCs. Single-cell RT-PCR indicated the expression of endophilins-A1-3 in IHCs, and immunoblotting confirmed the presence of endophilin-A1 and endophilin-A2 in the cochlea.
View Article and Find Full Text PDFToxoplasma gondii infects virtually any nucleated cell type of warm-blooded animals and humans including skeletal muscle cells (SkMCs). Infection of SkMCs by T. gondii, differentiation from the highly replicative tachyzoites to dormant bradyzoites and tissue cyst formation are crucial for parasite persistence in muscle tissue.
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