ArticleProceedings of the National Academy of Sciences of the United States of America2004
Membrane-associated guanylate kinase-like properties of beta-subunits required for modulation of voltage-dependent Ca2+ channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
- CaThe Journal of physiology · 2024Article
- β subunits of voltage-gated calcium channels in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Selective posttranslational inhibition of CaNature communications · 2022Article
- Adrenergic Regulation of Calcium Channels in the Heart.Annual review of physiology · 2022Review
- Adrenergic CaCirculation research · 2021Article
- Article
- Role of a conserved glutamine in the function of voltage-gated CaThe Journal of biological chemistry · 2018Article
- Down-regulation of the Wnt/β-catenin signaling pathway by Cacnb4.Molecular biology of the cell · 2017Article
- Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- The mammalian skeletal muscle DHPR has larger CaCell calcium · 2017Article
- Cloning and characterization of mersacidin like bacteriocin from Bacillus licheniformis MKU3 in Escherichia coli.Journal of food science and technology · 2016Article
- Alternative splicing generates a novel truncated Cav1.2 channel in neonatal rat heart.The Journal of biological chemistry · 2015Article
- Article
- Forskolin Regulates L-Type Calcium Channel through Interaction between Actinin 4 and β3 Subunit in Osteoblasts.PloS one · 2015Article
- The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.The Journal of cell biology · 2014Article
- Structure-function of proteins interacting with the α1 pore-forming subunit of high-voltage-activated calcium channels.Frontiers in physiology · 2014Review
- Structure and function of the β subunit of voltage-gated Ca²⁺ channels.Biochimica et biophysica acta · 2013Review
- Regulation of voltage-dependent calcium channels by RGK proteins.Biochimica et biophysica acta · 2013Review
- Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches.Pharmacological research · 2013Review
- Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy.The EMBO journal · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-voltage-activated Ca2+ channels regulate diverse functions ranging from muscle contraction to synaptic transmission. Association between auxiliary beta- and distinct pore-forming alpha1-subunits is obligatory for forming functional high-voltage-activated Ca2+ channels, yet the structural determinants underlying this interaction remain poorly understood. Recently, homology modeling of Ca(2+)-channel beta1b-subunit identified src homology 3 (SH3) and guanylate kinase (GK) motifs in a tandem arrangement reminiscent of the membrane-associated guanylate kinase (MAGUK) class of scaffolding proteins. However, direct evidence for MAGUK-like properties and their functional implications in beta-subunits is lacking. Here, we show a functional requirement for both SH3 and GK domains in beta2a. Point mutations in either the putative beta2a SH3 or GK domains severely blunted modulation of recombinant L-type channels, showing the importance of both motifs for a functional alpha1-beta interaction. Coexpression of these functionally deficient beta2a-SH3 and GK mutants rescued WT currents, demonstrating trans complementation similar to that observed in MAGUKs. Truncated "hemi-beta2a" subunits, containing either the SH3 or GK domain, were ineffective on their own, but reconstituted WT currents when coexpressed. Moreover, the SH3 and GK domains were found to interact in vitro. These findings reveal MAGUK-like properties in beta-subunits that are critical for alpha1-subunit modulation, revise current models of alpha1-beta association, and predict new physiological dimensions of beta-subunit function.
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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.