Furin Functions as a Nonproteolytic Chaperone for Matrix Metalloproteinase-28: MMP-28 Propeptide Sequence Requirement

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Matrix metalloproteinase-28 (MMP-28) is a secreted proteinase implicated in various physiological and pathological processes.
• The precise mechanisms governing MMP-28 secretion and function remain incompletely understood.

Purpose of the Study:

• To elucidate the role of furin in the secretion of MMP-28.
• To investigate the interaction between furin and MMP-28.

Main Methods:

• Utilized COS-1 cells transfected with MMP-28 cDNA.
• Investigated the effect of coexpressing MMP-28 with furin cDNA on protein secretion.
• Performed co-immunoprecipitation and co-immunolocalization studies.
• Assessed MMP-28-induced cell migration.

Main Results:

• MMP-28 protein levels were low in conditioned media compared to cell lysates.
• Coexpression with furin significantly enhanced MMP-28 secretion.
• Furin interacted with the propeptide domain of MMP-28, acting as an intermolecular chaperone.
• Cleavage at the furin consensus sequence was not required; proteolytically inactive furin also enhanced secretion.
• Furin and MMP-28 co-immunoprecipitated and were partially co-localized in the cytoplasm.
• Furin cotransfection enhanced MMP-28-induced cell migration.

Conclusions:

• Furin serves as a novel intermolecular chaperone for MMP-28 secretion.
• This furin-MMP-28 interaction provides a new mechanism for MMP-28 function.
• The findings offer insights into the regulation of MMP-28 activity in cellular processes.