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

Abstract

Calcineurin is responsible for mediating a wide variety of cellular processes in response to dynamic calcium (Ca 2+ ) 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 Ca 2+ oscillations in modulating calcineurin activity dynamics in insulin-secreting MIN6 β-cells. We show that Ca 2+ oscillations induce distinct temporal patterns of calcineurin activity in the cytosol and plasma membrane vs 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.

Función de la fosfatasa calcineurina en la citocinesis de Schizosaccharomyces pombe

“…La calcineurina desfosforila a los aminoácidos serina o treonina de forma poco selectiva, por lo que es necesario un fuerte control de su activación e inhibición para dar especificidad a su señalización. Este control está mediado por picos transitorios de calcio que se unen a los dominios EF-hand de la calcineurina B y de la calmodulina (Mehta et al, 2014). La calcineurina B posee 4 dominios EF-hand, de estos, los sitios 3 y el 4 presentan una mayor afinidad por la calmodulina, mientras que la de los sitios 1 y 2 es inferior (Gallagher et al, 2001;Kakalis et al, 1995).…”