The first-in-class cell-permeant fluorescent probe provides direct and visual evidence of SARM1 activation in axonal degeneration and identified the first covalent, allosteric inhibitor of SARM1 acting on the NAD-binding pocket in the ARM domain.
An in-depth metagenomic analysis of possibly the most abundant and widespread microbial lineage in the surface ocean teases apart evolutionary processes that maintain its genomic heterogeneity and biogeography.
Cryo-EM shows that the NADase activity of SARM1 is allosterically inhibited by physiological concentrations of NAD+ that stabilizes an auto-inhibited conformation of SARM1, explaining how NAD+ depletion may inflict neurodegeneration.
Axonal metabolic flux analysis demonstrates that expression of NMNAT1 blocks axonal degeneration in cultured mouse neurons not by altering NAD+ synthesis, but rather by inhibiting injury-induced, SARM1-dependent NAD+ consumption.
A structure of the complete, membrane bound, COPII coat solved by sub-tomogram averaging reveals the arrangement of all protein subunits on the membrane and suggests a mechanism for coating heterogeneously-shaped carriers.