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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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,...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

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,...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

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 homology) domains...

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Related Experiment Video

Updated: May 28, 2026

Pull-down of Calmodulin-binding Proteins
07:51

Pull-down of Calmodulin-binding Proteins

Published on: January 23, 2012

Kv7 channels can function without constitutive calmodulin tethering.

Juan Camilo Gómez-Posada1, Paloma Aivar, Araitz Alberdi

  • 1Unidad de Biofísica, Consejo Superior de Investigaciones Científicas-Universidad del País Vasco/Euskal Herriko Unibersitatea, Leioa, Spain.

Plos One
|October 8, 2011
PubMed
Summary

Calmodulin binding is essential for Kv7 channel function, but a specific mutation allows calmodulin-independent activity. This finding challenges the view of calmodulin as a mandatory auxiliary subunit for Kv7 channels.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Ion Channel Physiology

Background:

  • Kv7 channels (Kv7.2-7.5) regulate neuronal excitability.
  • Calmodulin binding is considered essential for Kv7 channel function.
  • Mutations disrupting calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC).

Purpose of the Study:

  • To investigate the role of calmodulin binding in Kv7 channel function.
  • To determine if calmodulin is an indispensable auxiliary subunit.
  • To explore the impact of specific mutations on calmodulin dependence.

Main Methods:

  • Site-directed mutagenesis of Kv7.2 subunits.
  • Electrophysiological recordings to assess channel function.
  • Analysis of calmodulin binding-independent activity.

Main Results:

  • A phosphomimetic mutation (S511D) in Kv7.2 allows for calmodulin-independent channel function.
  • This mutation demonstrates that Kv7 channels can be functional without constitutive calmodulin tethering.
  • The findings challenge the established role of calmodulin as a strictly required auxiliary subunit.

Conclusions:

  • Constitutive calmodulin tethering is not universally required for Kv7 channel function.
  • Kv7 channel activity can be modulated independently of calmodulin binding under certain conditions.
  • This research refines our understanding of Kv7 channel regulation and its implications for epilepsy.