Junctophilins: Key Membrane Tethers in Muscles and Neurons

Piggott, Christopher A.; Jin, Yishi

doi:10.3389/fnmol.2021.709390

Cited by 13 publications

(8 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The T-tubule and sarcoplasmic reticulum (SR) membrane contact sites called dyad junctions, analogous to the vertebrate triad junctions, mediate local calcium dynamics for excitation-contraction coupling along sarcomeres (Peachey, 1968, Smith, 1966). As an indicator of the dyads, we detected Junctophilin (Jp), a conserved SR-anchored junction protein (Calpena et al, 2018, Piggott and Jin, 2021, Takeshima et al, 2000). In wildtype muscle, Jp localized as expected to uniformly-distributed foci associated with both SR and T-tubule membranes (marked by Rtnl1 and Dlg1, respectively; Figure 3A-3B; Supplemental Figure S3A ).…”

Section: Resultsmentioning

confidence: 99%

PI(4,5)P₂role in Transverse-tubule membrane formation and muscle function

Fujita,

Girada,

Vogler

et al. 2024

Preprint

View full text Add to dashboard Cite

Transverse (T)-tubules, the vast, tubulated domains of the muscle plasma membrane, are critical to maintain healthy skeletal and heart contractions. How the intricate T-tubule membranes are formed is not well understood, with challenges to systematically interrogate in muscle. We established the use of intact Drosophila larval body wall muscles as an ideal system to discover mechanisms that sculpt and maintain the T-tubule membrane network. A muscle-targeted genetic screen identified specific phosphoinositide lipid regulators necessary for T-tubule organization and muscle function. We show that a PI4KIIIalpha-Skittles/PIP5K pathway is needed for T-tubule localized PI(4)P to PI(4,5)P2 synthesis, T-tubule organization, calcium regulation, and muscle and heart rate functions. Muscles deficient for PI4KIIIalpha or Amphiphysin, the homolog of human BIN1, similarly exhibited specific loss of transversal T-tubule membranes and dyad junctions, yet retained longitudinal membranes and the associated dyads. Our results highlight the power of live muscle studies, uncovering distinct mechanisms and functions for sub-compartments of the T-tubule network relevant to human myopathy.

show abstract

Section: Resultsmentioning

confidence: 99%

PI(4,5)P₂role in Transverse-tubule membrane formation and muscle function

Fujita,

Girada,

Vogler

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…If CaV1 and RyR function in the same vesicle fusion pathway, they should be colocalized (Piggott & Jin, 2021). RyR was tagged with HALO at the N-terminus of the neuronal isoform (Extended Data Figure 4C) (Marques et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles

Mueller

Merrill

Watanabe

et al. 2022

Preprint

View full text Add to dashboard Cite

Activation of voltage-gated calcium channels at synapses leads to local increases in calcium and the fusion of synaptic vesicles. However, presynaptic output will be determined by the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at C. elegans neuromuscular junctions, CaV2, and CaV1 mediate the release of two distinct pools of synaptic vesicles. Superresolution microscopy demonstrates that CaV2 channels are concentrated in densely packed clusters ~300 nm in diameter with active zone proteins Neurexin, α-Liprin, SYDE, ELKS, RIMB, α Catulin, and MAGI. The CaV2 channels mediate the fusion of vesicles docked within 100 nm of the dense projection and is colocalized with to the synaptic vesicle priming protein UNC 13L. By contrast, CaV1 channels are dispersed in the synaptic varicosity and are coupled to internal calcium stores via the ryanodine receptor. The CaV1 and ryanodine receptor mediate the fusion of vesicles docked broadly in the synaptic varicosity and are colocalized with the vesicle priming protein UNC-13S. These distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.

show abstract

“…These observations indicate that JPH2 is essential for the formation of CRUs in the heart, at both dyads and peripheral couplings. In addition to this tethering role, JPH2 also facilitates communication between RyR2 and Ca v 1.2 at these CRUs [86]. Recently, it was demonstrated that the joining region of JPH2 interacts directly with Ca v 1.2, recruiting the LTCC to the cardiac dyad [87].…”

Section: (B) Junctophilinsmentioning

confidence: 99%

Evolution of the cardiac dyad

Mackrill

2022

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Cardiac dyads are the site of communication between the sarcoplasmic reticulum (SR) and infoldings of the sarcolemma called transverse-tubules (TT). During heart excitation–contraction coupling, Ca 2+ -influx through L-type Ca 2+ channels in the TT is amplified by release of Ca 2+ -from the SR via type 2 ryanodine receptors, activating the contractile apparatus. Key proteins involved in cardiac dyad function are bridging integrator 1 (BIN1), junctophilin 2 and caveolin 3. The work presented here aims to reconstruct the evolutionary history of the cardiac dyad, by surveying the scientific literature for ultrastructural evidence of these junctions across all animal taxa; phylogenetically reconstructing the evolutionary history of BIN1; and by comparing peptide motifs involved in TT formation by this protein across metazoans. Key findings are that cardiac dyads have been identified in mammals, arthropods and molluscs, but not in other animals. Vertebrate BIN1 does not group with members of this protein family from other taxa, suggesting that invertebrate BINs are paralogues rather orthologues of this gene. Comparisons of BIN1 peptide sequences of mammals with those of other vertebrates reveals novel features that might contribute to TT and dyad formation. The analyses presented here suggest that the cardiac dyad evolved independently several times during metazoan evolution: an unexpected observation given the diversity of heart structure and function between different animal taxa. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.

show abstract

Junctophilins: Key Membrane Tethers in Muscles and Neurons

Cited by 13 publications

References 69 publications

PI(4,5)P₂role in Transverse-tubule membrane formation and muscle function

PI(4,5)P₂role in Transverse-tubule membrane formation and muscle function

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles

Evolution of the cardiac dyad

Contact Info

Product

Resources

About

Junctophilins: Key Membrane Tethers in Muscles and Neurons

Cited by 13 publications

References 69 publications

PI(4,5)P2role in Transverse-tubule membrane formation and muscle function

PI(4,5)P2role in Transverse-tubule membrane formation and muscle function

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles

Evolution of the cardiac dyad

Contact Info

Product

Resources

About

PI(4,5)P₂role in Transverse-tubule membrane formation and muscle function

PI(4,5)P₂role in Transverse-tubule membrane formation and muscle function