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Research Article Free access | 10.1172/JCI116609

Secretory protein traffic. Chromogranin A contains a dominant targeting signal for the regulated pathway.

R J Parmer, X P Xi, H J Wu, L J Helman, and L N Petz

Department of Medicine, University of California, San Diego, La Jolla 92161.

Find articles by Parmer, R. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California, San Diego, La Jolla 92161.

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Department of Medicine, University of California, San Diego, La Jolla 92161.

Find articles by Wu, H. in: JCI | PubMed | Google Scholar

Department of Medicine, University of California, San Diego, La Jolla 92161.

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Department of Medicine, University of California, San Diego, La Jolla 92161.

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First published August 1, 1993 - More info

Published in Volume 92, Issue 2 on August 1, 1993
J Clin Invest. 1993;92(2):1042–1054. https://doi.org/10.1172/JCI116609.
© 1993 The American Society for Clinical Investigation
First published August 1, 1993 - Version history
Abstract

Secretory proteins are targeted into either constitutive (secreted upon synthesis) or regulated (stored in vesicles and released in response to a secretagogue) pathways. To investigate mechanisms of protein targeting into catecholamine storage vesicles (CSV), we stably expressed human chromogranin A (CgA), the major soluble protein in human CSV, in the rat pheochromocytoma PC-12 cell line. Chromaffin cell secretagogues (0.1 mM nicotinic cholinergic agonist, 55 mM K+, or 2 mM Ba++) caused cosecretion of human CgA and catecholamines from human CgA-expressing cells. Sucrose gradients colocalized human CgA and catecholamines to subcellular particles of the same buoyant density. Chimeric proteins, in which human CgA (either full-length [457 amino acids] or truncated [amino-terminal 226 amino acids]) was fused in-frame to the ordinarily nonsecreted protein chloramphenicol acetyltransferase (CAT), were expressed transiently in PC-12 cells. Both constructs directed CAT activity into regulated secretory vesicles, as judged by secretagogue-stimulated release. These data demonstrate that human CgA expressed in PC-12 cells is targeted to regulated secretory vesicles. In addition, human CgA can divert an ordinarily non-secreted protein into the regulated secretory pathway, consistent with the operation of a dominant targeting signal for the regulated pathway within the peptide sequence of CgA.

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