ArticleMolecular biology of the cell2014
Mutations that disrupt Ca²⁺-binding activity endow Doc2β with novel functional properties during synaptic transmission.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Synaptotagmin 7 docks synaptic vesicles to support facilitation and Doc2α-triggered asynchronous release.eLife · 2024Article
- Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains.Frontiers in endocrinology · 2024Article
- Mechanisms of Synaptic Vesicle Exo- and Endocytosis.Biomedicines · 2022Review
- The role of the C2A domain of synaptotagmin 1 in asynchronous neurotransmitter release.PloS one · 2020Article
- Doc2b CaScientific reports · 2019Article
- Article
- Doc2-mediated superpriming supports synaptic augmentation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs.eLife · 2017Article
- Phosphatidylinositol (4, 5)-bisphosphate targets double C2 domain protein B to the plasma membrane.Traffic (Copenhagen, Denmark) · 2017Article
- Structural characterization of the Rabphilin-3A-SNAP25 interaction.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Loss of Doc2-Dependent Spontaneous Neurotransmission Augments Glutamatergic Synaptic Strength.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Structural elements that underlie Doc2β function during asynchronous synaptic transmission.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Molecular underpinnings of synaptic vesicle pool heterogeneity.Traffic (Copenhagen, Denmark) · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Double C2-domain protein (Doc2) is a Ca(2+)-binding protein implicated in asynchronous and spontaneous neurotransmitter release. Here we demonstrate that each of its C2 domains senses Ca(2+); moreover, the tethered tandem C2 domains display properties distinct from the isolated domains. We confirm that overexpression of a mutant form of Doc2β, in which two acidic Ca(2+) ligands in the C2A domain and two in the C2B domain have been neutralized, results in markedly enhanced asynchronous release in synaptotagmin 1-knockout neurons. Unlike wild-type (wt) Doc2β, which translocates to the plasma membrane in response to increases in [Ca(2+)](i), the quadruple Ca(2+)-ligand mutant does not bind Ca(2+) but is constitutively associated with the plasma membrane; this effect is due to substitution of Ca(2+) ligands in the C2A domain. When overexpressed in wt neurons, Doc2β affects only asynchronous release; in contrast, Doc2β Ca(2+)-ligand mutants that constitutively localize to the plasma membrane enhance both the fast and slow components of synaptic transmission by increasing the readily releasable vesicle pool size; these mutants also increase the frequency of spontaneous release events. Thus, mutations in the C2A domain of Doc2β that were intended to disrupt Ca(2+) binding result in an anomalous enhancement of constitutive membrane-binding activity and endow Doc2β with novel functional properties.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.