ArticleProceedings of the National Academy of Sciences of the United States of America2012
Membrane-localized β-subunits alter the PIP2 regulation of high-voltage activated Ca2+ channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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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.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
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- ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.The Journal of general physiology · 2023Article
- Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Acute phosphatidylinositol 4,5 bisphosphate depletion destabilizes sarcolemmal expression of cardiac L-type CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of Lysosomal Cholesterol in Regulating PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Molecular basis of the PIPeLife · 2022Article
- Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury.ACS central science · 2022Article
- Modality specific roles for metabotropic GABAergic signaling and calcium induced calcium release mechanisms in regulating cold nociception.Frontiers in molecular neuroscience · 2022Article
- Regulatory effects of protein S-acylation on insulin secretion and insulin action.Open biology · 2021Review
- Control of Neuronal Excitability by Cell Surface Receptor Density and Phosphoinositide Metabolism.Frontiers in pharmacology · 2021Article
- Cutting out the fat: Site-specific deacylation of an ion channel.The Journal of biological chemistry · 2020Article
- MARCKS mediates vascular contractility through regulating interactions between voltage-gated CaVascular pharmacology · 2020Article
- Palmitoylation of the KProceedings of the National Academy of Sciences of the United States of America · 2020Article
- PIPPhysiological reports · 2019Article
- Emerging roles for multifunctional ion channel auxiliary subunits in cancer.Cell calcium · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The β-subunits of voltage-gated Ca(2+) (Ca(V)) channels regulate the functional expression and several biophysical properties of high-voltage-activated Ca(V) channels. We find that Ca(V) β-subunits also determine channel regulation by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)). When Ca(V)1.3, -2.1, or -2.2 channels are cotransfected with the β3-subunit, a cytosolic protein, they can be inhibited by activating a voltage-sensitive lipid phosphatase to deplete PIP(2). When these channels are coexpressed with a β2a-subunit, a palmitoylated peripheral membrane protein, the inhibition is much smaller. PIP(2) sensitivity could be increased by disabling the two palmitoylation sites in the β2a-subunit. To further test effects of membrane targeting of Ca(V) β-subunits on PIP(2) regulation, the N terminus of Lyn was ligated onto the cytosolic β3-subunit to confer lipidation. This chimera, like the Ca(V) β2a-subunit, displayed plasma membrane localization, slowed the inactivation of Ca(V)2.2 channels, and increased the current density. In addition, the Lyn-β3 subunit significantly decreased Ca(V) channel inhibition by PIP(2) depletion. Evidently lipidation and membrane anchoring of Ca(V) β-subunits compete with the PIP(2) regulation of high-voltage-activated Ca(V) channels. Compared with expression with Ca(V) β3-subunits alone, inhibition of Ca(V)2.2 channels by PIP(2) depletion could be significantly attenuated when β2a was coexpressed with β3. Our data suggest that the Ca(V) currents in neurons would be regulated by membrane PIP(2) to a degree that depends on their endogenous β-subunit combinations.
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