Research Article

Nrg1 Intracellular Signaling Is Neuroprotective upon Stroke

Figure 1

NRG1 phylogenetic conservation and expression in aging. (a) Sequence alignment of the transmembrane and intracellular regions of NRG1 that are crucial for intracellular signaling, namely, the transmembrane domain (in light-blue), the nuclear localization signal (in red), and the phosphorylation sites (green circles). The black arrowhead indicates the location of the Val-to-Leu (rs7494201) schizophrenia-linked mutation that affects gamma-secretase processing and Nrg1 intracellular signaling. The red arrowheads indicate the amino acids in the nuclear localization signal required for the nuclear targeting of Nrg1-ICD. The grey arrowhead indicates the site of the Met-to-Thr mutation, rs10503929, while the white arrowhead indicates a primate-specific polymorphism. CRD: cysteine-rich domain; EGF: epithelial growth factor domain; TM: transmembrane domain. (b) Forest plot showing the correlation -score between age and mRNA expression for NRG1 and ERBB4 in four independent datasets (Tgen, ; BrainEqtl, ; HBTRC, ; BrainCloud, ). Meta-analysis conducted at the gene level employing Stouffer’s weighted -score.