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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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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
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Enzyme-linked Receptors01:00

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Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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Updated: Jun 9, 2025

Strategies for Assessing Autistic-Like Behaviors in Mice
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Strategies for Assessing Autistic-Like Behaviors in Mice

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Convergence on CaMK4: A Key Modulator of Autism-Associated Signaling Pathways in Neurons.

Jacqueline Kaiser1, Alana Risteska2, Abbey G Muller3

  • 1Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Melbourne, Victoria, Australia; St. Vincent's Institute of Medical Research, Melbourne, Victoria, Australia; Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.

Biological Psychiatry
|October 23, 2024
PubMed
Summary

Defects in the CaMK4 signaling pathway may contribute to autism spectrum disorder (ASD). This review highlights genetic and environmental factors affecting CaMK4, suggesting it as a potential therapeutic target for ASD.

Keywords:
AutismIntellectual disabilityKinaseNeurodevelopmentPsychiatrySignaling

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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Autism spectrum disorder (ASD) has complex genetic underpinnings, with over 1000 identified rare genetic variations.
  • Genetic heterogeneity in ASD has hindered the identification of common therapeutic targets for core and comorbid traits.
  • Genes associated with ASD often encode proteins crucial for brain development, signal transduction, and synaptic transmission.

Purpose of the Study:

  • To review the role of CAMK4 (calcium/calmodulin-dependent protein kinase 4) and its signaling pathway in autism pathogenesis.
  • To explore genetic variants in CAMK4 and other genes impacting the CaMK4 pathway in relation to ASD.
  • To examine environmental factors influencing CaMK4 signaling in preclinical and clinical autism models.

Main Methods:

  • Literature review of genetic variations in CAMK4 and associated genes.
  • Analysis of studies on environmental risk factors impacting CaMK4 signaling.
  • Synthesis of molecular, genetic, physiological, and environmental evidence.

Main Results:

  • Identified 3 likely pathogenic CAMK4 variants in individuals with hyperkinetic movement disorder and comorbid ASD.
  • Noted 4 additional CAMK4 variations associated with ASD and 12 variations in other genes affecting CaMK4 signaling.
  • Highlighted 3 environmental risk factors impacting CaMK4 signaling in autism models and cohorts.

Conclusions:

  • Evidence suggests the CaMK4 signaling pathway plays a significant role in a common autism pathogenesis network.
  • CAMK4 is proposed as a potential therapeutic target for autism spectrum disorder.
  • Understanding CaMK4 signaling offers insights into ASD etiology and treatment development.