Sorting of growth hormone-erythropoietin fusion proteins in rat salivary glands.
Neuroendocrine and exocrine cells secrete proteins in either a constitutive manner or via the regulated secretory pathway (RSP), but the specific sorting mechanisms involved are not fully understood. After gene transfer to rat salivary glands, the transgenic model proteins human growth hormone (hGH) and erythropoietin (hEpo) are secreted primarily into saliva (RSP; exocrine) and serum (constitutive; endocrine), respectively. We hypothesized that fusion of hGH at either the C-terminus or the N-terminus of hEpo would re-direct hEpo from the bloodstream into saliva. We constructed and expressed two fusion proteins, hEpo-hGH and hGH-hEpo, using serotype 5-adenoviral vectors, and delivered them to rat submandibular glands in vivo via retroductal cannulation. Both the hEpo-hGH and hGH-hEpo fusion proteins, but not hEpo alone, were secreted primarily into saliva (p<0.0001 and p=0.0083, respectively). These in vivo studies demonstrate for the first time that hGH, in an N- as well as C-terminal position, influences the secretion of a constitutive pathway protein.
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, USA. ysamuni@mail.nih.gov
Yuval
Y
Samuni
Changyu
C
Zheng
Niamh X
NX
Cawley
Ana P
AP
Cotrim
Y Peng
YP
Loh
Bruce J
BJ
Baum
D000818:Animals; D030801:Animals, Genetically Modified; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D021381:Protein Transport; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism*; D019076:Transgenes
D011993:Recombinant Fusion Proteins; D004921:Erythropoietin; D013006:Growth Hormone