The N-terminal Domain Tethers the Voltage-gated Calcium Channel β2e-subunit to the Plasma Membrane via Electrostatic and Hydrophobic Interactions

Miranda-Laferte, Erick; Ewers, David; Guzman, Raul E.; Jordan, Nadine; Schmidt, Silke; Hidalgo, Patricia

doi:10.1074/jbc.m113.507244

Cited by 31 publications

(36 citation statements)

References 37 publications

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“…Membrane-associated proteins themselves may also insert structural elements into the membrane to better carry out their function [30–33]. This includes antimicrobial peptides, which are thought embed into the membrane and generate a pore-like structure that kills the target [34], as well as other signaling or metabolic proteins that depend on access to membrane-embedded substrates, and may anchor themselves to the membrane via electrostatic or hydrophobic interactions [35–37]. …”

Section: Membrane Activity Is a Critical Factor In The Biology Of Smamentioning

confidence: 99%

The cellular membrane as a mediator for small molecule interaction with membrane proteins

Mayne

Arcario

Mahinthichaichan

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The cellular membrane constitutes the first element that encounters a wide variety of molecular species to which a cell might be exposed. Hosting a large number of structurally and functionally diverse proteins associated with this key metabolic compartment, the membrane not only directly controls the traffic of various molecules in and out of the cell, it also participates in such diverse and important processes as signal transduction and chemical processing of incoming molecular species. In this article, we present a number of cases where details of interaction of small molecular species such as drugs with the membrane, which are often experimentally inaccessible, have been studied using advanced molecular simulation techniques. We have selected systems in which partitioning of the small molecule with the membrane constitutes a key step for its final biological function, often binding to and interacting with a protein associated with the membrane. These examples demonstrate that membrane partitioning is not only important for the overall distribution of drugs and other small molecules into different compartments of the body, it may also play a key role in determining the efficiency and the mode of interaction of the drug with its target protein.

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Section: Membrane Activity Is a Critical Factor In The Biology Of Smamentioning

confidence: 99%

The cellular membrane as a mediator for small molecule interaction with membrane proteins

Mayne

Arcario

Mahinthichaichan

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…These fragments were then cloned into the PGEX-6P1 (GE Healthcare, Freiburg, Germany) vector and verified by sequencing. GST-fusion proteins (GST-NT ClC-3b, GST-NT ClC-3b S3/S2/S1 , and GST alone) were expressed in Escherichia coli (BL21) for 4 -5 h at 30°C after induction with isopropyl ␤-D-1-thiogalactopyranoside (IPTG) and purified using affinity and size-exclusion chromatography as described previously (27,28). For pull-down experiments brain lysates were produced by homogenization of brain tissue from C57Bl/6 mice and two consecutive rounds of centrifugation.…”

Section: Methodsmentioning

confidence: 99%

Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions

Guzman

Miranda-Laferte²,

Franzen

et al. 2015

Journal of Biological Chemistry

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Background: Alternative splicing can result in proteins with distinct subcellular distributions and functions. Results: Three ClC-3 splice variants are expressed in the mammalian brain with different subcellular localizations, but identical transport properties. Conclusion: Differences in the subcellular localization of ClC-3 splice variants suggest diverse cellular functions. Significance: The existence of multiple splice variants needs to be considered when studying cellular functions of ClC-3.

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“…33 A previous study suggested a possibility that as with MARCKS, the 3 Ser/Thr residues in the N-terminal region of b2e could be target sites for phosphorylation by PKC and phosphorylation of the residues may induce dissociation of the subunit from the plasma membrane. 11 However, with a PKC activator, our data revealed that PKC activation had no effect on the location change of b2e, indicating that membrane localization of the b2e subunit mainly depends on anionic membrane phospholipids. Even though extensive tests are needed to demonstrate the possible phosphorylation of b2e, this result shows that unlike MARCKS, the activation of PKC has no influence on the location change of b2e.…”

Section: Discussionmentioning

confidence: 61%

“…9,10 Recent studies showed that the b2e subunit is associated with the plasma membrane through electrostatic interaction, while b2a is tethered to the plasma membrane through palmitoylation in the N-terminus. [11][12][13] In particular, membrane phosphoinositides (PIs) are involved in the association with several basic amino acid residues in the N-terminus of the b2e subunit, leading to the possibility that the location of the b2e subunit can be changed by membrane PI dynamics.…”

Section: Introductionmentioning

confidence: 99%

Differential interaction of β2e with phosphoinositides: A comparative study between β2e and MARCKS

Kim

Suh

2016

Channels

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Voltage-gated calcium (Ca V ) channels are responsible for Ca 2C influx in excitable cells. As one of the auxiliary subunits, the Ca V b subunit plays a pivotal role in the membrane expression and receptor modulation of Ca V channels. In particular, the subcellular localization of the b subunit is critical for determining the biophysical properties of Ca V channels. Recently, we showed that the b2e isotype is tethered to the plasma membrane. Such a feature of b2e is due to the reversible electrostatic interaction with anionic membrane phospholipids. Here, we further explored the membrane interaction property of b2e by comparing it with that of myristoylated alanine-rich C kinase substrate (MARCKS). First, the charge neutralization of the inner leaf of the plasma membrane induced the translocation of both b2e and MARCKS to the cytosol, while the transient depletion of poly-phosphoinositides (poly-PIs) by translocatable pseudojanin (PJ) systems induced the cytosolic translocation of b2e but not MARCKS. Second, the activation of protein kinase C (PKC) induced the translocation of MARCKS but not b2e. We also found that after the cytosolic translocation of MARCKS by receptor activation, depletion of poly-PIs slowed the recovery of MARCKS to the plasma membrane. Together, our data demonstrate that both b2e and MARCKS bind to the membrane through electrostatic interaction but with different binding affinity, and thus, they are differentially regulated by enzymatic degradation of membrane PIs.

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The N-terminal Domain Tethers the Voltage-gated Calcium Channel β2e-subunit to the Plasma Membrane via Electrostatic and Hydrophobic Interactions

Cited by 31 publications

References 37 publications

The cellular membrane as a mediator for small molecule interaction with membrane proteins

The cellular membrane as a mediator for small molecule interaction with membrane proteins

Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions

Differential interaction of β2e with phosphoinositides: A comparative study between β2e and MARCKS

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