Pulsed SILAM Reveals In Vivo Dynamics of Murine Brain Protein Translation

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.