RESUMEN
Introduction: Oligodendrocyte progenitor cells (OPCs) are vital for neuronal myelination and remyelination in the central nervous system. While the molecular mechanisms involved in OPCs' differentiation and maturation are not completely understood, GABA is known to positively influence these processes through the activation of GABAA receptors (GABAARs). The molecular identity of GABAARs expressed in human OPCs remains unknown, which restricts their specific pharmacological modulation to directly assess their role in oligodendrocytes' maturation and remyelination. Methods: In this study, we conducted a transcriptomic analysis to investigate the molecular stoichiometry of GABAARs in OPCs from the human brain. Using eight available transcriptomic datasets from the human brain cortex of control individuals, we analyzed the mRNA expression of all 19 known GABAARs subunit genes in OPCs, with variations observed across different ages. Results: Our analysis indicated that the most expressed subunits in OPCs are α1-3, ß1-3, γ1-3, and ε. Moreover, we determined that the combination of any α with ß2 and γ2 is likely to form heteropentameric GABAARs in OPCs. Importantly, we also found a strong correlation between GABAAR subunits and transcripts for postsynaptic scaffold proteins, suggesting the potential postsynaptic clustering of GABAARs in OPCs. Discussion: This study presents the first transcriptional-level identification of GABAAR subunits expressed in human OPCs, providing potential receptor combinations. Understanding the molecular composition of GABAARs in OPCs not only enhances our knowledge of the underlying mechanisms in oligodendrocyte maturation but also opens avenues for targeted pharmacological interventions aimed at modulating these receptors to promote remyelination in neurological disorders.
RESUMEN
Protein phosphorylation is regulated by the activity of enzymes generically known as kinases. One of those kinases is Mitogen-Activated Protein Kinases (MAPK), which operate through a phosphorylation cascade conformed by members from three related protein kinase families namely MAPK kinase kinase (MEKK), MAPK kinase (MEK), and MAPK; these three acts hierarchically. Establishing the evolution of these proteins in the plant kingdom is an interesting but complicated task because the current MAPK, MAPKK, and MAPKKK subfamilies arose from duplications and subsequent sub-functionalization during the early stage of the emergence of Viridiplantae. Here, an in silico genomic analysis was performed on 18 different plant species, which resulted in the identification of 96 genes not previously annotated as components of the MAPK (70) and MEK (26) families. Interestingly, a deeper analysis of the sequences encoded by such genes revealed the existence of putative domains not previously described as signatures of MAPK and MEK kinases. Additionally, our analysis also suggests the presence of conserved activation motifs besides the canonical TEY and TDY domains, which characterize the MAPK family.
