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Calmodulin-dependent Signaling

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,...

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Updated: Jun 20, 2025

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

Morphotype-specific calcium signaling in human microglia.

Sofia Nevelchuk¹, Bianca Brawek¹, Niklas Schwarz²

¹Department of Neurophysiology, Institute of Physiology, Eberhard Karls University of Tübingen, Keplerstr. 15, 72074, Tübingen, Germany.

Journal of Neuroinflammation

|July 17, 2024

Summary

Human microglia exhibit compartmentalized calcium (Ca2+) signals, with distinct properties varying by cell shape and location. This reveals crucial differences from rodent models, impacting brain health research.

Keywords:

Human microglia In vitro human brain tissue model Morphotypes of resident microglia Native microglial microenvironment microRNA-9-assisted labeling

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Last Updated: Jun 20, 2025

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Published on: January 30, 2014

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Published on: April 8, 2022

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Published on: September 19, 2012

Area of Science:

Neuroscience
Cell Biology
Neuroimmunology

Background:

Microglia, the brain's immune cells, use calcium (Ca2+) signaling to monitor neural activity and detect damage.
Ca2+ dyshomeostasis is implicated in neurological disorders in mice, but human microglial Ca2+ signaling remains uncharacterized.

Purpose of the Study:

To investigate the in situ Ca2+ signaling properties of human microglia within their native microenvironment.
To characterize the differences in Ca2+ signal compartmentalization and properties across human microglial morphotypes.

Main Methods:

Development of a novel genetically-encoded ratiometric Ca2+ indicator for human microglia.
Analysis of Ca2+ signaling in freshly resected human brain tissue and organotypic slice cultures.
In situ monitoring of Ca2+ signaling in aged human microglia.

Main Results:

Human microglial Ca2+ signals are compartmentalized, with distinct properties in different cellular compartments and morphotypes.
Basal Ca2+ levels are lower in ramified microglia and higher in ameboid microglia.
Signal dynamics (fraction of active cells, signal amplitude/duration) vary significantly across microglial morphotypes (ramified, hypertrophic, ameboid).

Conclusions:

Human microglia display unique, compartmentalized Ca2+ signaling patterns not previously observed.
Differences in Ca2+ signaling across morphotypes suggest functional specialization within the human microglia population.
These findings provide a foundation for understanding human microglial roles in health and disease.