ArticleProceedings of the National Academy of Sciences of the United States of America2005
The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of alpha2delta subunits is key to trafficking voltage-gated Ca2+ channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 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
134 citing papers in PubMed, 226 citations in OpenAlex.
- Trial
- Synaptic Ca2+ channels and neurexins are linked through direct and indirect binding complexes.Scientific reports · 2026Article
- Cardiac α2δ1 C-terminal contributes to left atrial hypertrophy in chronic ischemic heart failure, in association with changes in membrane GluN1 and p-CAMKII/p-HDAC4 signaling.Cell and tissue research · 2026Article
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Role of the C-terminal domain in modifying pH-dependent regulation of CaChannels (Austin, Tex.) · 2025Article
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- Bioinformatic discovery of type 11 secretion system (T11SS) cargo across theMicrobial genomics · 2025Article
- α2δ-2 regulates synaptic GluK1 kainate receptors in Purkinje cells and motor coordination.Brain : a journal of neurology · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.Biochemical Society transactions · 2025Review
- Alpha-neurexins in health and disease.Frontiers in molecular neuroscience · 2025Review
- A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel-dependent as well as synaptic functions of αJournal of neurochemistry · 2025Article
- Ion Channels in Odor Information Processing of Neural Circuits of the Vertebrate Olfactory Bulb.International journal of molecular sciences · 2024Review
- Autism-Linked Mutations in αPharmaceuticals (Basel, Switzerland) · 2024Article
- Pin1 promotes human CaCell communication and signaling : CCS · 2024Article
- Deciphering the enigmatic PilY1 ofBiochemistry and biophysics reports · 2024Article
- Structural bases of inhibitory mechanism of CaNature communications · 2024Article
- Loss of the auxiliary αJBMR plus · 2024Article
- The importance of cache domains in αChannels (Austin, Tex.) · 2023Article
- Active Zone Trafficking of CaV2/UNC-2 Channels Is Independent of β/CCB-1 and α2δ/UNC-36 Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
All auxiliary alpha2delta subunits of voltage-gated Ca2+ (Ca(V)) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in alpha2delta-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the alpha2delta-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant alpha2delta-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT alpha2delta-2, the MIDAS mutant alpha2delta-2 subunit did not enhance and, in some cases, further diminished Ca(V)1.2, -2.1, and -2.2 currents coexpressed with beta1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant alpha2delta-2 reduced surface expression and strongly increased the perinuclear retention of Ca(V)alpha1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108-15 cells. Despite the presence of endogenous alpha2delta subunits, heterologous expression of alpha2delta-2 in differentiated NG108-15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that alpha2delta subunits normally interact with the Ca(V)alpha1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the alpha2delta subunit is required to promote trafficking of the alpha1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains.
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.