Neuronal membrane proteasome-derived peptides modulate NMDAR-dependent neuronal signaling to promote changes in gene expression.

ABSTRACT: The neuronal membrane proteasome (NMP) degrades intracellular proteins into peptides that are released directly into the extracellular space, whereby they stimulate neurons to promote signaling mechanisms that remain unknown. Here, we demonstrate that neuronal stimulation promotes NMP activity and, subsequently, enhanced production of NMP peptides. We show that these neuronal activity-dependent NMP peptides can rapidly promote N-methyl-D-aspartate receptor (NMDAR)-dependent calcium influx in neurons. This leads to sustained phosphorylation of the well-defined stimulus-induced transcription factor, cyclic AMP response element (CRE)-binding protein (CREB). Downstream of these events, we identified changes to neuronal target genes which included increased expression of immediate early genes (

SUBMITTER: Turker F 

PROVIDER: S-EPMC10881162 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature