Pulsed SILAM reveals in vivo dynamics of murine brain protein translation

Abstract

Identification of proteins that are synthesized de novo in response to specific microenvironmental cues is critical for understanding molecular mechanisms that underpin vital physiological processes and pathologies. Here, we report that a brief period of SILAM (Stable Isotope Labeling of Mammals) diet enables the determination of biological functions corresponding to actively translating proteins in the mouse brain. Our results demonstrate that the synapse, dendrite, and myelin sheath are highly active neuronal structures that display rapid protein synthesis, producing key mediators of chemical signaling as well as nutrient sensing, lipid metabolism, and amyloid precursor protein processing/stability. Together, these findings confirm that protein metabolic activity varies significantly between brain functional units in vivo. Our data indicate that pulsed SILAM approaches can unravel complex protein expression dynamics in the murine brain and identify active synthetic pathways and associated functions that are likely impaired in neurodegenerative diseases.