Junctional trafficking and restoration of retrograde signaling by the cytoplasmic RyR1 domain

Polster, Alexander; Perni, Stefano; Filipova, Dilyana; Moua, Ong; Ohrtman, Joshua D.; Bichraoui, Hicham; Beam, Kurt G.; Papadopoulos, Symeon

doi:10.1085/jgp.201711879

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…All the constructs contain the eight-residue sequence DYKDDDDK (FLAG tag) either at the N terminus (JPH1 and JPH2) or at the C terminus (JPH3 and JPH4) based on sequencing by GenScript and confirmed in our laboratory. mCherry-JPH1 and mCherry-JPH2 were made from the intermediate constructs YFP-JPH1 and YFP-JPH2, which were made by cutting YFP-RYR1 ( Polster et al, 2018 ) with HindIII and XbaI and inserting the fragment produced from the GenScript clones for either JPH1 or JPH2 cut with the same two enzymes (thus replacing the RYR1 coding sequence). mCherry-JPH1 and mCherry-JPH2 were then obtained by excising the PciI-BsrGI fragment of YFP-JPH1 or YFP-JPH2, which includes the cytomegalovirus enhancer-promoter and YFP, and replacing it with the PciI-BsrGI fragment from mCherry-C1 (ref.…”

Section: Methodsmentioning

confidence: 99%

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Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

Perni

Beam

2022

Journal of General Physiology

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In skeletal muscle, depolarization of the plasma membrane (PM) causes conformational changes of the calcium channel CaV1.1 that then activate RYR1 to release calcium from the SR. Being independent of extracellular calcium entry, this process is termed voltage-induced calcium release. In skeletal muscle, junctophilins (JPHs) 1 and 2 form the SR–PM junctions at which voltage-induced calcium release occurs. Previous work demonstrated that JPH2 is able to recapitulate voltage-induced calcium release when expressed in HEK293 cells together with CaV1.1, β1a, Stac3, and RYR1. However, it is unknown whether JPH1 and the more distantly related neuronal JPH3 and JPH4 might also function in this manner, a question of interest because different JPH isoforms diverge in their interactions with RYR1. Here, we show that, like JPH2, JPH1 and JPH3, coexpressed with CaV1.1, β1a, Stac3, and RYR1 in HEK293 cells, cause colocalization of CaV1.1 and RYR1 at ER–PM junctions. Furthermore, potassium depolarization elicited cytoplasmic calcium transients in cells in which WT CaV1.1 was replaced with the calcium impermeant mutant CaV1.1(N617D), indicating that JPH1, JPH2, and JPH3 can all support voltage-induced calcium release, despite sequence divergence and differences in interaction with RYR1. Conversely, JPH4-induced ER–PM junctions contain CaV1.1 but not RYR1, and cells expressing JPH4 are unable to produce depolarization-induced calcium transients. Thus, JPHs seem to act primarily to form ER–PM junctions and to recruit the necessary signaling proteins to these junctions but appear not to be directly involved in the functional interactions between these proteins.

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Section: Methodsmentioning

confidence: 99%

“…The expression plasmids for CFP- and YFP-Ca V 1.1 ( Papadopoulos et al, 2004 ), unlabeled β1a and Stac3 ( Polster et al, 2015 ), and YFP-RYR1 ( Polster et al, 2018 ) were previously described.…”

Section: Methodsmentioning

confidence: 99%

Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

Perni

Beam

2022

Journal of General Physiology

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“…Thus, skeletal muscle SR-PM junctions are the structural platforms for transmission of excitation from PM to SR. Signaling at triads is bidirectional, as physical interaction between RyRs and DHPRs also enhances Ca V 1.1 activity (12,14) and slow voltage-gated Ca 2+ current (I Ca ) activation kinetics (14,15). That a mechanical linkage mediates retrograde RyR1-to-DHPR signaling was demonstrated by its restoration by expression of only the N-terminal cytosolic portion of RyR1 (RyR1 1:4300 ) that lacks the ion channel-forming segments in RyR1-null dyspedic myotubes (14).…”

Section: Endoplasmic Reticulum-plasma Membrane Junctions In Muscle Cellsmentioning

confidence: 99%

Endoplasmic Reticulum–Plasma Membrane Junctions as Sites of Depolarization-Induced Ca²⁺Signaling in Excitable Cells

Dixon

Trimmer

2023

Annu. Rev. Physiol.

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Membrane contact sites between endoplasmic reticulum (ER) and plasma membrane (PM), or ER-PM junctions, are found in all eukaryotic cells. In excitable cells they play unique roles in organizing diverse forms of Ca2+ signaling as triggered by membrane depolarization. ER-PM junctions underlie crucial physiological processes such as excitation-contraction coupling, smooth muscle contraction and relaxation, and various forms of activity-dependent signaling and plasticity in neurons. In many cases the structure and molecular composition of ER-PM junctions in excitable cells comprise important regulatory feedback loops linking depolarization-induced Ca2+ signaling at these sites to the regulation of membrane potential. Here, we describe recent findings on physiological roles and molecular composition of native ER-PM junctions in excitable cells. We focus on recent studies that provide new insights into canonical forms of depolarization-induced Ca2+ signaling occurring at junctional triads and dyads of striated muscle, as well as the diversity of ER-PM junctions in these cells and in smooth muscle and neurons. Expected final online publication date for the Annual Review of Physiology, Volume 85 is February 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…The rabbit RyR1 construct N-terminally tagged with GFP was described by Lorenzon et al (2001) (41). The construction of the N-terminally labeled constructs EYFP-RyR1, ECFP-RyR1 and RyR1 1:4300 (in which the coding sequence for RyR1 terminates at amino acid 4300) was also described previously (24). Unlabeled RyR1, used for generating stable cell lines, was created by cutting the RyR1 sequence of EYFP-RyR1 with HindIII and MfeI and ligating it into the pCEP4 plasmid cut with the same two enzymes.…”

Section: Ryr Constructsmentioning

confidence: 99%

Neuronal junctophilins recruit specific CaV and RyR isoforms to ER-PM junctions and functionally alter CaV2.1 and CaV2.2

Perni

Beam

2021

eLife

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Despite their recognized physiological importance, the molecular architecture of ER-PM junctions induced by neuronal junctophilins (JPH3 and JPH4) is still poorly understood and challenging to address in neurons. This is due to the small size of the junctions and to the multiple isoforms of candidate junctional proteins in different brain areas. Using colocalization of tagged proteins expressed in tsA201 cells, and electrophysiology, we compared the interactions of JPH3 and JPH4 with different calcium channels. We found that JPH3 and JPH4 caused junctional accumulation of all the tested high-voltage-activated CaV isoforms, but not a low-voltage-activated CaV. Also, JPH3 and JPH4 noticeably modify CaV2.1 and CaV2.2 inactivation rate. RyR3 moderately colocalized at junctions with JPH4, whereas RyR1 and RyR2 did not. By contrast, RyR1 and RyR3 strongly colocalized with JPH3, and RyR2 moderately. Likely contributing to this difference, JPH3 binds to cytoplasmic domain constructs of RyR1 and RyR3, but not of RyR2.

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Junctional trafficking and restoration of retrograde signaling by the cytoplasmic RyR1 domain

Abstract: Type 1 RyRs (RyR1s) of the sarcoplasmic reticulum signal bidirectionally with plasma membrane dihydropyridine receptors in skeletal muscle. Polster et al. show that isolated cytoplasmic domains of RyR1 can oligomerize, localize to membrane junctions, and restore retrograde signaling.

Cited by 4 publications

References 41 publications

Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

Endoplasmic Reticulum–Plasma Membrane Junctions as Sites of Depolarization-Induced Ca²⁺Signaling in Excitable Cells

Neuronal junctophilins recruit specific CaV and RyR isoforms to ER-PM junctions and functionally alter CaV2.1 and CaV2.2

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Junctional trafficking and restoration of retrograde signaling by the cytoplasmic RyR1 domain

Abstract: Type 1 RyRs (RyR1s) of the sarcoplasmic reticulum signal bidirectionally with plasma membrane dihydropyridine receptors in skeletal muscle. Polster et al. show that isolated cytoplasmic domains of RyR1 can oligomerize, localize to membrane junctions, and restore retrograde signaling.

Cited by 4 publications

References 41 publications

Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

Endoplasmic Reticulum–Plasma Membrane Junctions as Sites of Depolarization-Induced Ca2+Signaling in Excitable Cells

Neuronal junctophilins recruit specific CaV and RyR isoforms to ER-PM junctions and functionally alter CaV2.1 and CaV2.2

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Endoplasmic Reticulum–Plasma Membrane Junctions as Sites of Depolarization-Induced Ca²⁺Signaling in Excitable Cells