Calmodulin-controlled spatial decoding of oscillatory Ca2+ signals by calcineurin

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Abstract

Calcineurin is responsible for mediating a wide variety of cellular processes in response to dynamic calcium (Ca²⁺) signals, yet the precise mechanisms involved in the spatiotemporal control of calcineurin signaling are poorly understood. Here, we use genetically encoded fluorescent biosensors to directly probe the role of cytosolic Ca²⁺ oscillations in modulating calcineurin activity dynamics in insulin-secreting MIN6 β-cells. We show that Ca²⁺ oscillations induce distinct temporal patterns of calcineurin activity in the cytosol and plasma membrane versus at the ER and mitochondria in these cells. Furthermore, we found that these differential calcineurin activity patterns are determined by variations in the subcellular distribution of calmodulin (CaM), indicating that CaM plays an active role in shaping both the spatial and temporal aspects of calcineurin signaling. Together, our findings provide new insights into the mechanisms by which oscillatory signals are decoded to generate specific functional outputs within different cellular compartments.

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Sohum Mehta

The Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Nwe-Nwe Aye-Han

The Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Ambhi Ganesan

The Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Laurel Oldach

The Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Kirill Gorshkov

The Johns Hopkins University School of Medicine, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Jin Zhang

The Johns Hopkins University School of Medicine, Baltimore, United States

For correspondence
jzhang32@jhmi.edu

Competing interests
The authors declare that no competing interests exist.

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