Aggregation and concentration-dependent sorting of exocrine regulated secretory proteins

Area of Science:

• Cell biology
• Molecular biology
• Biochemistry

Background:

• The regulated secretory pathway (RSP) is crucial for secreting specific proteins in endocrine and exocrine cells.
• Protein aggregation is hypothesized to be a key mechanism for sorting proteins into the RSP in exocrine cells.

Purpose of the Study:

• To investigate the aggregation behavior of exocrine secretory proteins, specifically amylase, and its role in sorting into the regulated secretory pathway.
• To determine the effect of protein expression levels, modulated by dexamethasone, on amylase sorting.

Main Methods:

• Studied aggregation properties of exocrine secretory proteins, including amylase, under physiological conditions.
• Utilized AR42J cells to assess amylase secretion and sorting.
• Stimulated secretion using substance P and cholecystokinin in cells treated with and without dexamethasone.

Main Results:

• Exocrine secretory proteins, including amylase, do not undergo homotypic aggregation in sorting organelles, contrary to prior hypotheses.
• Amylase does not aggregate with chondroitin sulfate, unlike other exocrine proteins.
• Amylase exhibits heterotypic aggregation, and its sorting into the regulated secretory pathway is enhanced by dexamethasone-induced expression stimulation.

Conclusions:

• Homotypic aggregation is not the mechanism for sorting exocrine secretory proteins into the regulated secretory pathway.
• Amylase sorting is concentration-dependent and can be significantly enhanced by increasing its expression via dexamethasone treatment.