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Biophysical Journal Jun 2023Synaptophysin (syp) is a major protein of secretory vesicles with four transmembrane domains (TMDs) and a large cytoplasmic C-terminus. Syp has been shown to regulate...
Synaptophysin (syp) is a major protein of secretory vesicles with four transmembrane domains (TMDs) and a large cytoplasmic C-terminus. Syp has been shown to regulate exocytosis, vesicle cycling, and synaptic plasticity through its C-terminus. However, the roles of its TMDs remain unclear. The TMDs of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are thought to line initial fusion pores, and structural work together with sequence analysis suggest that TMD III of syp may play a similar role. To test this hypothesis, we performed tryptophan scanning experiments of TMD III in chromaffin cells and used amperometry to evaluate fusion pores. In contrast to SNARE TMDs, tryptophan substitutions in syp TMD III had no effect on the flux through initial fusion pores. However, a number of these mutants increased the fraction of kiss-and-run events and decreased the initial fusion pore lifetime. These results indicate that TMD III stabilizes the initial fusion pore and controls the initial choice between kiss and run and full fusion. Late-stage fusion pores were not impacted by TMD III mutations. These results indicate that syp TMD III does not line the initial fusion pore. However, its impact on pore dynamics suggests that it interacts with a SNARE protein implicated as a part of the fusion pore that forms at the onset of exocytosis.
Topics: Synaptophysin; Tryptophan; Membrane Fusion; Exocytosis; SNARE Proteins
PubMed: 36168290
DOI: 10.1016/j.bpj.2022.09.029 -
Applied Immunohistochemistry &... Oct 2021This paper is number 8 in a series developed through a partnership between ISIMM and NordiQC with the purpose of reporting research assessing the performance...
This paper is number 8 in a series developed through a partnership between ISIMM and NordiQC with the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.
Topics: Humans; Immunoassay; Laboratory Proficiency Testing; Quality Control; Synaptophysin
PubMed: 34545849
DOI: 10.1097/PAI.0000000000000975 -
Traffic (Copenhagen, Denmark) Mar 2014Synaptobrevin II (sybII) is a key fusogenic molecule on synaptic vesicles (SVs) therefore the active maintenance of both its conformation and location in sufficient... (Review)
Review
Synaptobrevin II (sybII) is a key fusogenic molecule on synaptic vesicles (SVs) therefore the active maintenance of both its conformation and location in sufficient numbers on this organelle is critical in both mediating and sustaining neurotransmitter release. Recently three proteins have been identified having key roles in the presentation, trafficking and retrieval of sybII during the fusion and endocytosis of SVs. The nerve terminal protein α-synuclein catalyses sybII entry into SNARE complexes, whereas the monomeric adaptor protein AP-180 is required for sybII retrieval during SV endocytosis. Overarching these events is the tetraspan SV protein synaptophysin, which is a major sybII interaction partner on the SV. This review will evaluate recent studies to propose working models for the control of sybII traffic by synaptophysin and other Sybtraps (sybII trafficking partners) and suggest how dysfunction in sybII traffic may contribute to human disease.
Topics: Animals; Humans; Monomeric Clathrin Assembly Proteins; Protein Binding; Protein Transport; R-SNARE Proteins; Synaptophysin; alpha-Synuclein
PubMed: 24279465
DOI: 10.1111/tra.12140 -
Developmental Psychobiology Mar 2021This study aims at investigating whether early stress interacts with brain injury due to neonatal hypoxia-ischemia (HI). To this end, we examined possible changes in...
This study aims at investigating whether early stress interacts with brain injury due to neonatal hypoxia-ischemia (HI). To this end, we examined possible changes in synaptophysin (SYN) and brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC) of maternally separated rats that were subsequently exposed to a HI episode. Rat pups (n = 11) were maternally separated during postnatal days 1 to 6 (3hr/day), while another group was left undisturbed (n = 11). On postnatal day 7, a subgroup (n = 12) from each postnatal manipulation was exposed to HI. Synaptophysin and BDNF expression was estimated in mPFC prelimbic and anterior cingulate subregions of the ipsilateral and contralateral to the occluded common carotid artery hemispheres. Maternally separated rats expressed significantly less BDNF and SYN in both hemispheres. Neonatal HI significantly reduced BDNF and SYN expression in the ipsilateral mPFC only and this reduction was not further altered by early stress. Our findings indicate the enduring negative effect of a short period of maternal separation on the expression of mPFC SYN and BDNF. They, also, reveal that the HI-associated decreases in these markers are limited to the ipsilateral mPFC and are not exacerbated by early stress. These decreases may have important functional implications given the role of prefrontal area in high-order cognition.
Topics: Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Hypoxia; Ischemia; Maternal Deprivation; Prefrontal Cortex; Rats; Stress, Psychological; Synaptophysin
PubMed: 32623722
DOI: 10.1002/dev.22011 -
Brain Pathology (Zurich, Switzerland) Jan 1993The nerve terminal of neurons is filled with small synaptic vesicles, specialized secretory organelles involved in the storage and release of neurotransmitters. The... (Review)
Review
The nerve terminal of neurons is filled with small synaptic vesicles, specialized secretory organelles involved in the storage and release of neurotransmitters. The synapsins are a family of four proteins that are the major peripheral proteins on the cytoplasmic face of synaptic vesicles. Synaptophysin is the major integral membrane protein of synaptic vesicles. The characterization of the synapsins and of synaptophysin during the last years has revealed exciting information about their structure, regulation and possible function. To understand the role of the synapsins and synaptophysin in the biology of a nerve cell means to elucidate the fundamental mechanism of brain function, the release of neurotransmitter.
Topics: Amino Acid Sequence; Animals; Cytoskeleton; Humans; Molecular Sequence Data; Neurotransmitter Agents; Protein Kinases; Synapsins; Synaptic Vesicles; Synaptophysin
PubMed: 7903586
DOI: 10.1111/j.1750-3639.1993.tb00729.x -
Head and Neck Pathology Sep 2021Glomus tumors (GTs) are uncommon benign tumors, accounting for <2% of all soft tissue tumors and usually occur within the dermis or subcutis of distal extremities....
Glomus tumors (GTs) are uncommon benign tumors, accounting for <2% of all soft tissue tumors and usually occur within the dermis or subcutis of distal extremities. Primary tracheal GT is rare, and to date less than 40 tracheal GTs have been reported. Tracheal GT usually present as a polypoidal mass. They express smooth muscle markers, and are negative for cytokeratin (CK) and neuroendocrine markers on immunohistochemistry (IHC). We here report a case of tracheal GT showing diffuse strong aberrant immunoexpression for synaptophysin, initially construed as carcinoid. Focal synaptophysin expression has been described in few gastric GTs, and a nasal GT. Diligent histomorphological examination and careful selection of IHC panel helps in clinching the diagnosis. Complete resection is the standard treatment of modality.
Topics: Adult; Biomarkers, Tumor; Carcinoid Tumor; Diagnosis, Differential; Glomus Tumor; Humans; Male; Synaptophysin; Tracheal Neoplasms
PubMed: 33025460
DOI: 10.1007/s12105-020-01230-3 -
Acta Histochemica Oct 2020
Topics: Adenocarcinoma of Lung; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Neoplasm Proteins; Synaptophysin
PubMed: 33066833
DOI: 10.1016/j.acthis.2020.151611 -
Bosnian Journal of Basic Medical... Oct 2021Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the...
Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the blood. Thus, both CT and CgA are immunohistochemical and serum markers for MTCs. MTC occurs in both sporadic and inheritable cases and the hallmark of inheritable cases in multiple endocrine neoplasm 2 (NEN2) is MTC. MEN2 cases represent 30% of MTCs through germline RET protooncogene mutation and occur in younger ages involving bilateral thyroid lobes. Sporadic cases are 70% of cases of solitary tumor and occur in older ages. CgA and synaptophysin (SPY) are the two, most widely used and reliable immunohistochemical markers for neuroendocrine tumors including MTCs. This study aimed to detect different immunohistochemical staining patterns for CgA and SPY between non-symptomatic small, microscopic lesions and invading larger aggressive tumors in both MEA2 cases and sporadic cases. There was different CgA and SPY immunostaining in MEA2 cases where small tumors (≤ 0.3 cm) were lesser immunostained for CgA and SPY, despite strong staining for CT, compared to the larger (≥ 0.5cm) tumors, stronger immunostained for CgA. There was also different CgA and SPY immunohistochemical staining in sporadic cases between small lesion (≤ 0.5 cm) and larger tumors (≥ 1.0cm). One small sporadic tumor (0.5 x 0.3 cm) was strongly and weakly, patchy (about 10% of tumor tissue) stained for CgA and SPY, respectively, while larger sporadic tumors were diffusely, stronger stained for CgA and SPY. Therefore, stronger CgA and SPY immunostaining for larger tumors in both MEA2 and sporadic cases may be used as independent aggressive immunohistochemical markers for MTCs.
Topics: Adolescent; Adult; Aged; Calcitonin; Carcinoma, Neuroendocrine; Chromogranin A; Female; Humans; Immunohistochemistry; Male; Middle Aged; Multiple Endocrine Neoplasia; Synaptophysin; Thyroid Gland; Thyroid Neoplasms; Young Adult
PubMed: 33485291
DOI: 10.17305/bjbms.2020.5407 -
Proceedings of the National Academy of... Jan 2002Synaptophysin is an abundant synaptic vesicle protein without a definite synaptic function. Here, we examined a role for synaptophysin in synapse formation in mixed...
Synaptophysin is an abundant synaptic vesicle protein without a definite synaptic function. Here, we examined a role for synaptophysin in synapse formation in mixed genotype micro-island cultures of wild-type and synaptophysin-mutant hippocampal neurons. We show that synaptophysin-mutant synapses are poor donors of presynaptic terminals in the presence of competing wild-type inputs. In homogenotypic cultures, however, mutant neurons display no apparent deficits in synapse formation compared with wild-type neurons. The reduced extent of synaptophysin-mutant synapse formation relative to wild-type synapses in mixed genotype cultures is attenuated by blockers of synaptic transmission. Our findings indicate that synaptophysin plays a previously unsuspected role in regulating activity-dependent synapse formation.
Topics: Animals; Cells, Cultured; Hippocampus; Mice; Models, Neurological; Mutation; Neurons; Synapses; Synaptic Transmission; Synaptophysin
PubMed: 11792847
DOI: 10.1073/pnas.022575999 -
Neuron Jun 2011Despite being the most abundant synaptic vesicle membrane protein, the function of synaptophysin remains enigmatic. For example, synaptic transmission was reported to be...
Despite being the most abundant synaptic vesicle membrane protein, the function of synaptophysin remains enigmatic. For example, synaptic transmission was reported to be completely normal in synaptophysin knockout mice; however, direct experiments to monitor the synaptic vesicle cycle have not been carried out. Here, using optical imaging and electrophysiological experiments, we demonstrate that synaptophysin is required for kinetically efficient endocytosis of synaptic vesicles in cultured hippocampal neurons. Truncation analysis revealed that distinct structural elements of synaptophysin differentially regulate vesicle retrieval during and after stimulation. Thus, synaptophysin regulates at least two phases of endocytosis to ensure vesicle availability during and after sustained neuronal activity.
Topics: Animals; Electric Stimulation; Endocytosis; Enzyme Inhibitors; Hippocampus; Macrolides; Membrane Potentials; Mice; Mice, Knockout; Neurons; Patch-Clamp Techniques; Synaptic Transmission; Synaptic Vesicles; Synaptophysin; Time Factors
PubMed: 21658579
DOI: 10.1016/j.neuron.2011.04.001