Sorting of proThyrotropin Releasing Hormone Peptides

Brown University, Providence RI

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Abstract

DESCRIPTION (provided by applicant): ProThyrotropin releasing hormone is a 26 kDa precursor protein that in rats produces five TRH peptides and up to seven other peptides. TRH is responsible for regulating thyroid hormone levels by stimulating TSH secretion from the pituitary. It is becoming clear that the other peptides produced by partial endoproteolysis of the precursor also possess unique biological functions. To fully understand the function of a prohormone one must grasp its regulation at the levels of transcription, biosynthesis, processing, and sorting. For proTRH, little is currently known about how the peptides derived from it are sorted and stored in secretory granules for regulated release. In this proposal proTRH will be mutated at critical positions and each mutant will be evaluated for defects in sorting within AtT20 cells, a model secretory cell line. This will be done to test the hypothesis that certain structural motifs of proTRH drive its sorting to the regulated secretory pathway.