RT info:eu-repo/semantics/article T1 Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating A1 Ghosh, Debapriya A1 Nieves-CintrĂ³n, Madeline A1 Tajada, Sendoa A1 Brust-Mascher, Ingrid A1 Horne, Mary C. A1 Hell, Johannes W. A1 Dixon, Rose E. A1 Santana, Luis F. A1 Navedo, Manuel F. 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. SN 0167-4889 YR 2018 FD 2018 LK https://uvadoc.uva.es/handle/10324/65819 UL https://uvadoc.uva.es/handle/10324/65819 LA spa NO Biochim Biophys Acta Mol Cell Res. 2018 Sep;1865(9):1341-1355. DS UVaDOC RD 09-oct-2024