A conserved alpha-helix at the amino terminus of prosomatostatin serves as a sorting signal for the regulated secretory pathway

The Journal of Biological Chemistry
R MouchantafY C Patel

Abstract

Mammalian prosomatostatin (PSST) contains the bioactive peptides SST-14 and SST-28 at the COOH-terminal end of the molecule and a putative sorting signal in the propeptide segment for targeting the precursor to the regulated secretory pathway. The NH(2)-terminal segment of PSST consists of an amphipathic alpha-helix, which has been totally conserved throughout vertebrate evolution. We have analyzed the PSST-(3--15) region for sorting function by alanine scanning and deletional mutagenesis. Mutants created were stably expressed in AtT-20 cells. Regulated secretion was studied by analyzing basal and stimulated release of SST-14 LI and by immunocytochemistry for staining of SST-14 LI in punctate granules. Deletion of the PSST-(3--15) segment blocked regulated secretion and rerouted PSST for constitutive secretion as unprocessed precursor. Alanine scanning mutagenesis identified the region Pro(5)--Gln(12) as being important in precursor targeting, with Leu(7) and Leu(11) being critical. Molecular modeling demonstrated that these two residues are located in close proximity on a hydrophobic surface of the alpha-helix. Disruption of the alpha-helix did not impair the ability of PSST to be processed at the COOH terminus to SST-14 and S...Continue Reading

References

Jan 30, 1992·Nature·J E Rothman, L Orci
Sep 1, 1990·Metabolism: Clinical and Experimental·R BenoitE J Mufson
Jan 31, 1991·Biochemical and Biophysical Research Communications·J S Kizer, A Tropsha
Feb 1, 1989·The Journal of Clinical Investigation·M RavazzolaL Orci
Jan 1, 1987·Annual Review of Cell Biology·T L Burgess, R B Kelly
Jan 15, 1974·Biochemistry·P Y Chou, G D Fasman
Jul 1, 1995·The Biochemical Journal·A S GalanopoulouY C Patel
Apr 7, 1995·The Journal of Biological Chemistry·L Song, L D Fricker
Apr 1, 1994·The Biochemical Journal·P A Halban, J C Irminger
Aug 1, 1993·The Journal of Clinical Investigation·R J ParmerL N Petz
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·M RavazzolaL Orci
Oct 11, 1996·The Journal of Biological Chemistry·J W CreemersJ C Hutton
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·F S Shen, Y P Loh
Mar 1, 2000·Trends in Biochemical Sciences·C CombetG Deléage
Sep 28, 2000·The Journal of Biological Chemistry·I JutrasT L Reudelhuber

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