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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA016875-02
Application #
6805242
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2003-09-29
Project End
2006-09-28
Budget Start
2004-09-29
Budget End
2005-09-28
Support Year
2
Fiscal Year
2004
Total Cost
$44,195
Indirect Cost
Name
Brown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Mulcahy, Lawrence R; Barker, Alison J; Nillni, Eduardo A (2006) Disruption of disulfide bond formation alters the trafficking of prothyrotropin releasing hormone (proTRH)-derived peptides. Regul Pept 133:123-33
Mulcahy, Lawrence R; Vaslet, Charles A; Nillni, Eduardo A (2005) Prohormone-convertase 1 processing enhances post-Golgi sorting of prothyrotropin-releasing hormone-derived peptides. J Biol Chem 280:39818-26