Protein Kinase C Activation Drives a Differentiation Program in an Oligodendroglial Precursor Model through the Modulation of Specific Biological Networks.

Marina Damato,Michel Salzet,Damiana Pieragostino,Maxence Wisztorski,Michele Maffia,Tristan Cardon,Isabelle Fournier,Ilaria Cicalini,Daniele Vergara

doi:10.3390/ijms22105245

Abstract

Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography–mass spectrometry (LC–MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.

Highlights

Introduction iationsSpecific molecular mechanisms control cellular identity in different biological systems through the involvement of internal and external factors
Analog Phorbol 12-Myristate 13-Acetate (PMA) that acts by inducing the activation of DAG-sensitive Protein kinase C (PKC) members
To determine its possible activation status after PMA treatment, we evaluated the phoscenter of this network, and several of our identified proteins are directly regulated by this phorylation of cofilin, a downstream substrate of Rho-associated protein kinase (ROCK), in PMA-treated and untreated kinase

Summary

Introduction

Introduction iationsSpecific molecular mechanisms control cellular identity in different biological systems through the involvement of internal and external factors. The intrinsic ability of a cell to respond to particular signals is defined as competence, and it is a necessary condition for cellular reprogramming During these processes, plenty of stimuli from the microenvironment result in patterns of tissue-specific and stepwise changes in gene and protein expression, triggering the activation of lineage markers via interconnected crosstalk among multiple signaling pathways and nuclear transcriptional factors [1,2]. Plenty of stimuli from the microenvironment result in patterns of tissue-specific and stepwise changes in gene and protein expression, triggering the activation of lineage markers via interconnected crosstalk among multiple signaling pathways and nuclear transcriptional factors [1,2] These molecular mechanisms represent potential targets for drug design and development, targeting and boosting strategic regulators of cell plasticity and reprogramming. PKC is best-known for triggering the Licensee MDPI, Basel, Switzerland

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