HYTANE-Identified Latrophilin-3 Cleavage by Meprin β Leads to Loss of the Interaction Domains DOI Creative Commons
Fred Armbrust, Kira Bickenbach,

Tomas Koudelka

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The metalloprotease meprin β is upregulated in neurons and astrocytes of Alzheimer's disease patients' brains. While the role as β-secretase amyloid precursor protein (APP) has been characterized, its broader substrate profile within brain remains largely unexplored. Hence, to identify additional substrates, we conducted N-terminomics lysates from mice overexpressing employing Hydrophobic Tagging-Assisted N-terminal Enrichment (HYTANE) strategy. We observed 3906 (82.2%) peptides identified seven new substrates that match terms localization cleavage specificity. Of note, show mild cognitive impairments caused by amyloidogenic APP processing alongside hyperactivity altered exploratory behavior seemingly independent cleavage. latrophilin-3 was particular interest, defects are associated with human. In well cellulo, validated latrophilin-3, resulting release two domains. These domains promote interactions neuronal proteins such fibronectin leucine-rich repeat transmembrane proteins, promoting adequate synapse formation. Thus, might affect synaptic integrity cleaving interaction potentially exacerbating phenotype.

Language: Английский

HYTANE-Identified Latrophilin-3 Cleavage by Meprin β Leads to Loss of the Interaction Domains DOI Creative Commons
Fred Armbrust, Kira Bickenbach,

Tomas Koudelka

et al.

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The metalloprotease meprin β is upregulated in neurons and astrocytes of Alzheimer's disease patients' brains. While the role as β-secretase amyloid precursor protein (APP) has been characterized, its broader substrate profile within brain remains largely unexplored. Hence, to identify additional substrates, we conducted N-terminomics lysates from mice overexpressing employing Hydrophobic Tagging-Assisted N-terminal Enrichment (HYTANE) strategy. We observed 3906 (82.2%) peptides identified seven new substrates that match terms localization cleavage specificity. Of note, show mild cognitive impairments caused by amyloidogenic APP processing alongside hyperactivity altered exploratory behavior seemingly independent cleavage. latrophilin-3 was particular interest, defects are associated with human. In well cellulo, validated latrophilin-3, resulting release two domains. These domains promote interactions neuronal proteins such fibronectin leucine-rich repeat transmembrane proteins, promoting adequate synapse formation. Thus, might affect synaptic integrity cleaving interaction potentially exacerbating phenotype.

Language: Английский

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