Related Experiment Video
Updated: Feb 24, 2026
05:56
Author Spotlight: Unraveling the Initial Activation of the Adaptive Immune Response for Therapeutic Intervention
Published on: October 4, 2024
1.6K
A T-type channel-calmodulin complex triggers αCaMKII activation
Hadhimulya Asmara1,2, Ileana Micu3,2, Arsalan P Rizwan1,2
1Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Molecular Brain
|August 13, 2017
Summary
Calmodulin (CaM) dynamically interacts with Cav3.1 channels, dissociating upon activity to activate alphaCaMKII. This reveals a novel signaling cascade initiated by T-type calcium channel activity.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Signaling
Background:
- Calmodulin (CaM) is a crucial signaling protein regulating diverse cellular functions.
- Low voltage-activated calcium channels (Cav3 family) mediate low threshold calcium influx.
- Cav3 channels were not previously known to interact with CaM.
Purpose of the Study:
- To investigate the interaction between CaM and Cav3.1 channels.
- To determine the role of Cav3 calcium influx in downstream signaling.
- To elucidate the mechanism of alphaCaMKII activation by T-type channels.
Main Methods:
- Co-immunoprecipitation assays to detect CaM-Cav3.1 association.
- Electrophysiological recordings to measure Cav3 channel activity.
- Biochemical assays to assess alphaCaMKII activation.
Main Results:
- A constitutive association between CaM and Cav3.1 channels at rest was identified.
- CaM dissociates from Cav3.1 channels in an activity-dependent and calcium-dependent manner.
- Cav3 calcium influx activates cytoplasmic alphaCaMKII, dependent on the Cav3.1 C-terminus.
Conclusions:
- T-type channel calcium influx triggers a novel dynamic interaction between CaM and Cav3.1.
- This interaction initiates a signaling cascade leading to alphaCaMKII activation.
- Cav3.1 channels play a previously unrecognized role in CaM-mediated signaling.
Related Concept Videos
01:16Calmodulin-dependent Signaling
6.7K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.7K
01:21G-Protein Gated Ion Channels
6.0K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
6.0K
01:25cAMP-dependent Protein Kinase Pathways
8.6K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.6K
01:26Tension Response at Adherens Junctions
3.7K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
3.7K
01:22Activation and Inactivation of G Proteins
11.8K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
11.8K
01:15Amplifying Signals via Second Messengers
8.9K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
8.9K