Meprin proteolytic complexes at the cell surface and in extracellular spaces.

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Meprins are metalloproteinases belonging to the astacin family and metzincin superfamily.
• They exist as homo- and hetero-oligomeric complexes of alpha and beta subunits.
• Meprins are located at the brush border membranes of kidney and intestinal epithelial cells, and are also found in leukocytes and cancer cells.

Purpose of the Study:

• To describe the structure, function, and localization of meprins.
• To highlight their role in cleaving various bioactive peptides and proteins.
• To explore their potential in shedding cell surface proteins and concentrating proteolytic activity.

Main Methods:

• Database predictions and initial experimental data were used.
• Analysis of meprin subunit composition and complex formation (dimeric, tetrameric, high-molecular-mass).
• Investigation of meprin localization and potential activation sites.

Main Results:

• Meprins cleave diverse substrates including hormones, cytokines, and extracellular matrix proteins.
• Meprins can shed proteins from the cell surface.
• Membrane-bound complexes range from 200-400 kDa, while secreted alpha-oligomers form 1-6 MDa complexes.
• Secreted meprin alpha complexes are latent zymogens that concentrate protease activity.

Conclusions:

• Meprins represent some of the largest extracellular proteases identified.
• Latent meprin complexes can non-destructively travel and deliver concentrated protease activity to specific sites.
• Meprins exemplify novel mechanisms for concentrating proteolytic activity at cell surfaces and extracellularly, crucial for their function.