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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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Autophagy01:27

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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
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Autophagic Cell Death01:18

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Delivery Pathways to the Lysosome01:36

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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mTOR Signaling and Cancer Progression03:03

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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Regulated Protein Degradation02:58

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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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Related Experiment Video

Updated: Sep 30, 2025

In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
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Regulation of basal autophagy by calmodulin availability.

Jennifer Giles1, Vanessa Lopez1, Elizabeth McConnaha1

  • 1Department of Physiology & Pharmacology, Des Moines University College of Osteopathic Medicine, IA, USA.

The FEBS Journal
|March 14, 2022
PubMed
Summary

Calmodulin (CaM) availability is essential for basal autophagy, a cellular degradation process. Inhibiting CaM disrupts autophagic flux and lysosomal function, highlighting CaM

Keywords:
autophagycalmodulincalmodulin antagonistschloroquinelysosomal acidification

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Macroautophagy (autophagy) is a fundamental cellular process for maintaining homeostasis by degrading cellular components.
  • Calmodulin (CaM), a Ca2+ sensor, regulates diverse cellular functions but its availability can be a limiting factor.
  • The role of CaM availability in regulating basal autophagy has not been previously established.

Purpose of the Study:

  • To investigate the hypothesis that CaM availability is a critical regulator of basal autophagy.
  • To elucidate the mechanism by which CaM influences autophagic flux and lysosomal function.

Main Methods:

  • Utilized CaM antagonists (W-7, trifluoperazine, CGS9343b) and chloroquine to assess effects on autophagy.
  • Measured autophagosome accumulation, autophagic flux, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) activity.
  • Employed competitive binding assays, Ca2+ manipulation, and CaM buffering with high-affinity CaM-binding proteins.

Main Results:

  • CaM antagonists and chloroquine inhibited basal autophagic flux and caused autophagosome accumulation, mimicking each other's effects.
  • These reagents increased AMPK activity but not mTOR activity, and chloroquine directly bound CaM in a Ca2+ -dependent manner.
  • CaM inhibition, rather than Ca2+ changes, was responsible for autophagy inhibition; CaM buffering increased lysosomal pH and LC3-II accumulation.

Conclusions:

  • CaM availability is a prerequisite for basal autophagy.
  • CaM regulates autophagy through mechanisms involving lysosomal pH and AMPK activation.
  • This study reveals a novel regulatory role for CaM in maintaining cellular homeostasis via autophagy.