Correction: CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons

Farina, Margherita; Bospoort, Rhea van de; He, Erkai; Persoon, Claudia M.; Weering, Jan R.T. van; Broeke, Jurjen H.; Verhage, Matthijs; Toonen, Robert J.

doi:10.7554/elife.12968

Cited by 18 publications

(27 citation statements)

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“…This distribution was skewed, with approximately 20% of the events occurring during the first two bursts of stimulation, 50% during the first six bursts and almost 5% during the last two bursts. This was comparable with mouse neurons, where 30% of the events occurred during the first two bursts (Figures 6D and 6E; Farina et al., 2015). Similar secretion efficiency and kinetics were obtained from a second batch of human iPSC-derived neurons (Figures S6G–S6K).…”

Section: Resultssupporting

confidence: 85%

“…Expression of a cargo-reporter previously optimized in rodent neurons, NPY-mCherry (Farina et al., 2015, van de Bospoort et al., 2012), consistently yielded a punctate distribution that co-localized extensively (90%) with the endogenous DCV marker, CgB (Rosa et al., 1985), and had trafficking characteristics similar to rodents (see below). Furthermore, fusion of many individual DCVs was detected using the NPY-mCherry reporter upon bursts of APs in a strictly Ca 2+ - and SNARE-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

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Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons

et al. 2017

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SummaryNeurons communicate by regulated secretion of chemical signals from synaptic vesicles (SVs) and dense-core vesicles (DCVs). Here, we investigated the maturation of these two secretory pathways in micro-networks of human iPSC-derived neurons. These micro-networks abundantly expressed endogenous SV and DCV markers, including neuropeptides. DCV transport was microtubule dependent, preferentially anterograde in axons, and 2-fold faster in axons than in dendrites. SV and DCV secretion were strictly Ca2+ and SNARE dependent. DCV secretion capacity matured until day in vitro (DIV) 36, with intense stimulation releasing 6% of the total DCV pool, and then plateaued. This efficiency is comparable with mature mouse neurons. In contrast, SV secretion capacity continued to increase until DIV50, with substantial further increase in secretion efficiency and decrease in silent synapses. These data show that the two secretory pathways can be studied in human neurons and that they mature differentially, with DCV secretion reaching maximum efficiency when that of SVs is still low.

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Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons

et al. 2017

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“…According to previous work in primary cultured neurons (Farina et al, 2015), immunohistofluorescence analysis in adult mouse slices revealed high levels of CAPS-1 (Supplemental Figure 4) supporting the notion that this protein is associated with neuronal LDCVs. As expected, CAPS-1 was broadly expressed in the hippocampus showing no particular cell-specificity.…”

Section: Resultssupporting

confidence: 75%

Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles

Ramírez-Franco

Munoz-Cuevas

Luján

et al. 2016

Front. Cell. Neurosci.

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Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.

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“…The CADPS gene (calcium-dependent activator protein for secretion 1) encodes a neuroendocrine-specific cytosolic and peripheral membrane protein that is required for Ca 2+ -regulated exocytosis of the secretory vesicle. This protein is expressed in fetal and adult brain as well as in neuroendocrine tissues, and it is an essential regulator of the synaptic and large core vesicles priming in mammalian neurons as well as in neuroendocrine cells [Brunk et al, 2009;Farina et al, 2015]. The PTPRG gene (protein tyrosine phosphatase, receptor type G) encodes a protein that is a member of the protein tyrosine phosphatase (PTP) family.…”

Section: Discussionmentioning

confidence: 99%

A New 3p14.2 Microdeletion in a Patient with Intellectual Disability and Language Impairment: Case Report and Review of the Literature

Parmeggiani¹,

Buldrini²,

Fini³

et al. 2018

Mol Syndromol

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Interstitial deletions of chromosome 3p are rare, and specific genotype-phenotype correlations cannot always be assessed. We report the case of a 3p14.2 proximal microdeletion in a 60-year-old female patient with mild intellectual disability, severe speech delay, and mild dysmorphism. An array-CGH analysis detected a 500-kb deletion in the 3p14.2 region, including FEZF2, CADPS, and PTPRG. FEZF2 and CADPS are known to network within the neurodevelopmental pathways. It is possible that their rearrangements lead to the phenotypic features observed in the patient, and therefore, they can be considered candidate genes responsible for such abnormalities.

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Correction: CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons

Cited by 18 publications

References 0 publications

Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons

Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC-Derived Neurons

Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles

A New 3p14.2 Microdeletion in a Patient with Intellectual Disability and Language Impairment: Case Report and Review of the Literature

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