Multi-omics Analysis Sheds Light on the Extracellular Role of PCMT1

Area of Science:

• Biochemistry
• Molecular Biology
• Proteomics

Background:

• Protein damage, including isoaspartate (isoD) modification, accumulates with age and disease.
• The enzyme protein-l-isoaspartate O-methyltransferase (PCMT1) repairs isoD residues, preventing aberrant protein function.
• PCMT1's function in non-neural tissues is largely unknown.

Purpose of the Study:

• To investigate the role of PCMT1 in non-neural tissues using a Pcmt1 knockout mouse model.
• To identify proteins and genes affected by the absence or overexpression of PCMT1.
• To explore the genome-proteome correlations and extracellular functions of PCMT1.

Main Methods:

• Utilized isoD-proteomics, global proteomics, and transcriptomics in Pcmt1 knockout (KO) and wild-type (WT) mice.
• Analyzed gene and protein expression changes in various KO tissues.
• Performed proteomic analysis on PCMT1-overexpressing cells.

Main Results:

• Significant gene and protein alterations were observed in KO tissues, particularly in extracellular and membrane-related categories.
• IsoD-modified proteins, primarily long-lived ones, increased in KO tissues.
• PCMT1 interacts with proteins involved in extracellular and membrane functions, suggesting a novel extracellular role.

Conclusions:

• PCMT1 plays vital roles in maintaining protein integrity in both physiological and stress conditions across various tissues.
• PCMT1 exhibits both shared and tissue-specific functions.
• This study uncovers a previously unrecognized extracellular function for PCMT1.