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Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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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.
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Smooth Muscle Contraction01:25

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Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
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Feedback Regulation of Calcium Concentration01:27

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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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Cross-bridge Cycle01:26

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As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
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Formation of Muscle Fibers from Myoblasts01:13

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De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
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Related Experiment Video

Updated: Dec 8, 2025

Pull-down of Calmodulin-binding Proteins
07:51

Pull-down of Calmodulin-binding Proteins

Published on: January 23, 2012

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The calmodulin redox sensor controls myogenesis.

Alex W Steil1, Jacob W Kailing1, Cade J Armstrong1

  • 1Department of Biology, University of Wisconsin-La Crosse, La Crosse, WI, United States of America.

Plos One
|September 17, 2020
PubMed
Summary

Oxidative stress impairs muscle regeneration during aging. Researchers found that modifying the calmodulin gene (CALM1) to mimic oxidation halted muscle cell differentiation, suggesting a target for age-related muscle degeneration.

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Area of Science:

  • Muscle biology and aging research
  • Cellular redox signaling
  • Molecular genetics

Background:

  • Muscle aging is characterized by reduced regeneration capacity following injury or disuse.
  • Oxidative stress is implicated in this decline, but specific redox sensors in muscle regeneration remain unidentified.
  • Calmodulin, a muscle regulatory protein, possesses methionine residues sensitive to oxidation, potentially affecting its function.

Purpose of the Study:

  • To investigate the role of oxidative modification of calmodulin in muscle regeneration.
  • To determine if mimicking methionine oxidation in calmodulin impacts myogenesis.
  • To identify potential molecular targets for combating age-related muscle degeneration.

Main Methods:

  • Utilized CRISPR-Cas9 gene editing in C2C12 mouse myoblasts to create CALM1 mutations (M109Q) mimicking methionine oxidation.
  • Assessed myoblast differentiation into myotubes upon induction of myogenesis.
  • Analyzed the expression of early and late myogenic regulatory factors and cell cycle withdrawal.

Main Results:

  • Myoblasts with the CALM1 M109Q mutation (in one or both alleles) failed to differentiate into myotubes.
  • Despite the presence of early myogenic factors, mutated cells did not withdraw from the cell cycle.
  • Expression of late myogenic factors was significantly impaired in mutated myoblasts.

Conclusions:

  • A single oxidative modification to the redox-sensitive protein calmodulin can arrest myogenesis.
  • This finding highlights calmodulin's critical role in muscle differentiation and regeneration.
  • Targeting calmodulin's redox state may offer a strategy to mitigate oxidative stress effects in aging muscle.