Atypical behavior of NFATc1 in cultured intercostal myofibers

Patrick Robison,Martin F Schneider,Erick O Hernández-Ochoa

doi:10.1186/2044-5040-4-1

Patrick Robison, Martin F Schneider + Show 1 more

Open Access

https://doi.org/10.1186/2044-5040-4-1

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Journal: Skeletal Muscle	Publication Date: Jan 3, 2014
Citations: 52	License type: cc-by

Affiliation: University of Maryland, Baltimore

Abstract

BackgroundThe NFATc transcription factor family is responsible for coupling cytoplasmic calcium signals to transcription programs in a wide variety of cell types. In skeletal muscle, these transcription factors control the fiber type in response to muscle activity. This excitation-transcription (E-T) coupling permits functional adaptation of muscle according to use. The activity dependence of these transcription programs is sensitive to the firing patterns of the muscle, not merely the period of activity, enabling a nuanced adaptation to various functional tasks.MethodsIsolated skeletal muscle fibers expressing exogenous fluorescent NFATc1 were studied by confocal microscopy under stimulation both with and without pharmacological inhibitors. Western blots of whole muscle lysates were also used.ResultsThis study investigates the activity dependent response of NFATc1 skeletal muscle fibers cultured from mice, comparing fibers of respiratory origin to muscles responsible for limb locomotion. Using patterns of stimulation known to strongly activate NFATc1 in the commonly cultured flexor digitorum brevis and soleus muscles, we have observed significant deactivation of NFATc1 in cultured intercostal muscle fibers. This effect is at least partially dependent on the action of JNK and CaMKII in intercostal fibers.ConclusionsOur findings highlight the role of lineage in the NFAT pathway, showing that the respiratory intercostal muscle fibers decode similar E-T coupling signals into NFAT transcriptional programs in a different manner from the more commonly studied locomotor muscles of the limbs.

Highlights

The NFATc transcription factor family is responsible for coupling cytoplasmic calcium signals to transcription programs in a wide variety of cell types
The equilibrium is dominated by the kinases casein kinase 1 (CK1), glycogen synthase kinase 3 (GSK3), and dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) [15], ensuring phosphorylation and nuclear exclusion/transcriptional inactivity
Reverse translocation Our initial observation that Nuclear factor of activated T-cells (NFATc1) showed abnormally high resting activation in cultured ItC fibers [24] leads us to examine the activity of NFATc1 in these fibers more closely

Summary

Introduction

The NFATc transcription factor family is responsible for coupling cytoplasmic calcium signals to transcription programs in a wide variety of cell types In skeletal muscle, these transcription factors control the fiber type in response to muscle activity. These transcription factors control the fiber type in response to muscle activity This excitation-transcription (E-T) coupling permits functional adaptation of muscle according to use. Activation of NFATc1 is determined by the phosphorylation state of a serine rich region (SRR) including 13 regulatory phosphorylation sites [12] and at least three serine-proline repeats (SP repeats) forming a phosphorylation-dependent target for the isomerase Pin1 [13] The phosphorylation of these sites controls a conformational change, exposing nuclear localization sequences when dephosphorylated and nuclear export sequences when phosphorylated [14]. It has been known for some time that the NFAT pathway is capable of distinguishing calcium signals of similar magnitude by frequency [9,10], an ability which is critical to appropriate adaptive responses

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