Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating

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4 Citations (Scopus)

Abstract

L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of CaV1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that CaV1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain CaV1.2 clustering, channel activity and cooperative gating. Our study suggests that CaV1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca2+ signals.

Original languageEnglish (US)
Pages (from-to)1341-1355
Number of pages15
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1865
Issue number9
DOIs
StatePublished - Sep 1 2018

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Regulator Genes
Muscle Contraction
Actin Cytoskeleton
Microtubules
Cluster Analysis
Cell Membrane
Gene Expression

Keywords

  • Coupled gating
  • In vivo imaging
  • Ion channels
  • Vesicles

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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title = "Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating",
abstract = "L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of CaV1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that CaV1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain CaV1.2 clustering, channel activity and cooperative gating. Our study suggests that CaV1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca2+ signals.",
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author = "Debapriya Ghosh and Madeline Nieves-Cintr{\'o}n and Sendoa Tajada and Ingrid Brust-Mascher and Horne, {Mary C.} and Hell, {Johannes W.} and Dixon, {Rose E.} and Santana, {Luis F.} and Navedo, {Manuel F.}",
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AU - Ghosh, Debapriya

AU - Nieves-Cintrón, Madeline

AU - Tajada, Sendoa

AU - Brust-Mascher, Ingrid

AU - Horne, Mary C.

AU - Hell, Johannes W.

AU - Dixon, Rose E.

AU - Santana, Luis F.

AU - Navedo, Manuel F.

PY - 2018/9/1

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N2 - L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of CaV1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that CaV1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain CaV1.2 clustering, channel activity and cooperative gating. Our study suggests that CaV1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca2+ signals.

AB - L-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of CaV1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that CaV1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of CaV1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain CaV1.2 clustering, channel activity and cooperative gating. Our study suggests that CaV1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca2+ signals.

KW - Coupled gating

KW - In vivo imaging

KW - Ion channels

KW - Vesicles

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