The role of eIF2B in eukaryotic protein synthesis: new insights from vanishing myelin Seminar

The eukaryotic translation initiation factor complex eIF2B is a key regulator of initiation of protein synthesis, acting as the guanine nucleotide exchange factor (GEF) for eIF2. Regulation of eIF2B is a key determinant of the rate of translation initiation in cells and is mediated primarily by phosphorylation of eIF2 in response to cellular stresses, including viral infection, nutrient deprivation and the accumulation of unfolded proteins.
Mutations in the genes encoding eIF2B have been shown to be the cause of the neurological leukodystrophy Vanishing White Matter, an autosomal recessive disorder that results in the degradation of central nervous system myelin.
I will be discussing how we have used these disease causing mutants, plus other targeted mutants, to further our understanding of eIF2B function, in particular focusing on how the eIF2B complex is assembled. I will present new insights into how formation of this complex may be crucial in modulating not just eIF2B function, but in the cellular stress responses mediated by eIF2.