Differential mRNA distribution of components of the ERK/MAPK signalling cascade in the adult mouse brain

Abstract

The mitogen-activated protein kinases (MAPKs), also called extracellular signal-regulated kinases (ERKs), are a group of serine/threonine terminal protein kinases activated downstream of a pleiotrophy of transmembrane receptors. Main intracellular components of the MAPK signalling pathway are the RAF, MEK, and ERK proteins, which work in a cascade of activator and effector proteins. They regulate many fundamental cellular functions, including cell proliferation, cell survival, and cell differentiation by transducing extracellular signals to cytoplasmic and nuclear effectors. To reveal more details about possible activation cascades in this pathway, the present study gives a complete description of the differential expression of Braf, Mek1, Mek2, Mek5, Erk1, Erk2, Erk3, and Erk5 in the adult murine brain by way of in situ hybridization analysis. In this study, we found that each gene is widely expressed in the whole brain, except for Mek2, but each displays a very distinct expression pattern, leading to distinct interactions of the MAPK components within different regions. Most notably we found that 1) Braf and Erk3 are coexpressed in the hippocampus proper, confirming a possible functional interaction; 2) in most forebrain areas, Mek5 and Erk5 are coexpressed; and 3) in the neurogenic regions of the brain, namely, the olfactory bulb and the dentate gyrus, Braf is absent, indicating that other activator proteins have to take over its function. Despite these differences, our results show widespread coexpression of the pathway components, thereby confirming the hypothesis of redundant functions among several MEK and ERK proteins in some regions of the brain.

Single and Combined Silencing of ERK1 and ERK2 Reveals Their Positive Contribution to Growth Signaling Depending on Their Expression Levels

“…For example, we have shown that in brain structures, expression ranged from up to 13-fold more ERK2 than ERK1 in the superficial cortex to only twice as much ERK2 than ERK1 in the medulla. These measurements correlated well with previous quantitative Western blotting experiments (31) and mRNA expression measured by in situ hybridization (13,24). In many experiments, silencing of ERK1 has no effects, probably because the abundant level of ERK2 can compensate for the loss of ERK1.…”

Activation of ERK/MAPK in the Lateral Amygdala of the Mouse is Required for Acquisition of a Fear-Potentiated Startle response

“…Our results showed that they are all present, allowing us to rule out a major difference between the mouse and the rat in the expression of these molecules, considered as the basis of amygdala-dependent neural processes leading to fear learning. Moreover, the relative abundance of all these four proteins with respect to the HPRT protein, used as loading control (data not shown), suggested that these ERK/MAPK signaling pathway members are not showing a major difference in their relative protein expression levels; this is in contrast with what we observed previously in an in situ hybridization study, where Mek2 was not detectable in most of the regions of the adult mouse brain (Di Benedetto et al, 2007). It could very well be the case that, in our previous study, the mRNA level for MEK2 was not high enough to be detected by ISH analysis, as it could be quickly translated and degraded; thus, making its level too low for detection through ISH, but allowing enough protein to be produced for detection through WB.…”

“…To our knowledge, it was never shown that these four MAPK signaling pathway components are coexpressed in the LA nucleus of the adult mouse brain. Interestingly, even though the mRNA for Mek2 was absent from most of the regions of the adult mouse brain, including the LA (Di Benedetto et al, 2007), at the protein level, it was present.…”

“…Although conditioned fear is strongly conserved across species, its molecular control may differ even in highly related species as the rat and the mouse. Indeed, we recently showed that the expression pattern of components of the MAPK pathway in adult rat and mouse brains can differ at the mRNA level (for a comparison, see Thomas andHunt, 1993 andDi Benedetto et al, 2007). Therefore, despite the well-described role of MAPKs in fear conditioning in rats, given their differential expression patterns in rat and mouse, the goal of this study was to investigate the role of MAPKs in fear conditioning in mice.…”

Targeted Inactivation of Mapk4 in Mice Reveals Specific Nonredundant Functions of Erk3/Erk4 Subfamily Mitogen-Activated Protein Kinases

“…Interestingly, the regional pattern of Erk4 expression differs from that of Erk3 in several regards. In contrast to Erk4, Erk3 mRNA is weakly expressed in the piriform cortex and is not detected in the olfactory bulb (8). In the hippocampus, the level of Erk3 is very weak in the CA1 region, and the dentate gyrus is devoid of signal, whereas clear expression of Erk4 is found in these regions.…”