Calcium Channel Biology (Prof. Dr. Patricia Hidalgo)

Über

Normal cell function relies on proteins working properly at the right place, at the right time and at the right amount. The “Calcium Channel Biology” research group aims at understanding the regulation and cellular impact of ionic and non-ionic functions of voltage-activated calcium channels along the intracellular life cycle of the channel protein; from their synthesis in the endoplasmic reticulum, along their transport to their site of function and during their lifespan at the plasma membrane to their removal.

Forschungsthemen

The multisubunit voltage-activated calcium channel opens in response to changes in the voltage across the membrane of excitable cells, allowing the entry of calcium, the ubiquitous intracellular messenger that regulates almost all aspects of cell function. The channel complex and its subunits also exhibit non-ionic functions that regulate cellular processes independent of ion permeation.

Our research seeks to elucidate the determinants underlying the functional plasticity and availability of these multi-tasking proteins, the role of post-translational modifications, and protein-protein interactions that reroute the subunits to different cellular pathways, and the mechanisms responsible for monitoring and clearing defective subunits. We also explore deregulation of these functions in cardiac and neurological disorders caused by genetic mutations in calcium channel subunits. We focus on the function of the Cavβ subunit on cardiac muscle cells in health and disease, using primary cultures from knock-out mice and human induced pluripotent stem cells (hiPSC)-derived cardiomyocytes.

To address these questions, we use a multidisciplinary approach combining molecular biology, protein biochemistry, proteomics and interactome analysis, gene-based downregulation, electrophysiology, and laser scanning and spinning disk microscopy to image calcium channels in living cells.

Kontakt

Prof. Dr. Patricia Hidalgo

IBI-1

Gebäude 15.21 / Raum 2035

+49 2461/61-84442

E-Mail
Calcium Channel Biology (Prof. Dr. Patricia Hidalgo)
The pore-forming CaVα1 subunit requires CaVβ-subunit (either co-expressed or covalently linked) to be delivery to the plasma membrane and mediate ionic currents. The figure shows macroscopic ion currents and laser scanning confocal images of cells transiently expressing different combinations of voltage-gated calcium channel subunits. Current traces elicited by voltage steps to -20 mV, 0 mV and +20 mV from holding potential of -90 mV are shown. Overlapping pixels between CaVα1 subunit (green) and the plasma membrane marker (magenta) are shown in white. mNG, mNeonGreen fluorescence protein.
Calcium Channel Biology (Prof. Dr. Patricia Hidalgo)
Tracking the intracellular movement of CaV channels. Time lapses images of fluorescently labelled CaV channels expressed in mammalian cells using high-time resolution microscopy. Single trajectories of the channel complex can be reconstituted from the time-lapse images to obtain information about the transport velocities of the channel inside the cell. The channel displays confined by diffusive-like motion combined with directed long-range movements resembling their active transport along a dense network of tubulin and actin filaments.
Calcium Channel Biology (Prof. Dr. Patricia Hidalgo)
The multisubunit voltage-gated calcium channel (CaV) complex. Following membrane depolarization CaVα1 opens allowing calcium influx into the cell, that in turn triggers multiple cellular responses.
Calcium Channel Biology (Prof. Dr. Patricia Hidalgo)
Fluorescently labelled HL-1 cardiomyocytes. Laser scanning images of HL-1 cells stained for microtubule (green) and actin cytoskeleton (red) tubulin filaments, and CaV1.2 calcium channel (blue). Picture by Rachel Schrammen
Calcium Channel Biology (Prof. Dr. Patricia Hidalgo)
Molecular model of CaVβ-actin interaction. The modelling was performed by integrating computational protein-protein docking with experimental data of chemical cross-linking mass spectrometry.

Members

Projekte

• Calcium channel subunits in breast cancer

• Characterization of new modulators of calcium channels from snake venom

• Ubiquitination and sumoylation in calcium channel subunits

• Role of Cavβ in cardiac fibrosis regulation via quantitative proteomics and interactome analysis.

• hiPSC-derived cardiomyocytes as models for cardiac muscle cells in health and disease

Publications
Research Software or other Community Services

Letzte Änderung: 29.11.2024