HYTANE-Identified Latrophilin-3 Cleavage by Meprin β Leads to Loss of the Interaction Domains.

ABSTRACT: The metalloprotease meprin β is upregulated in neurons and astrocytes of Alzheimer's disease patients' brains. While the role of meprin β as the β-secretase of amyloid precursor protein (APP) has been characterized, its broader substrate profile within the brain remains largely unexplored. Hence, to identify additional substrates, we conducted N-terminomics of brain lysates from mice overexpressing meprin β in astrocytes employing the Hydrophobic Tagging-Assisted N-terminal Enrichment (HYTANE) strategy. We observed 3906 (82.2%) N-terminal peptides and identified seven new substrates that match meprin β in terms of localization and cleavage specificity. Of note, the meprin β overexpressing mice show mild cognitive impairments caused by amyloidogenic APP processing alongside hyperactivity an

SUBMITTER: Armbrust F 

PROVIDER: S-EPMC11976865 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature