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J. Biol. Chem., Vol. 280, Issue 6, 4803-4807, February 11, 2005

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Modulation of Secretory Granule-targeting Efficiency by Cis and Trans Compounding of Sorting Signals^*

Marie-Josée Lacombe, Chantal Mercure, Jimmy D. Dikeakos, and Timothy L. Reudelhuber

From the Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada

Several protein domains acting through seemingly different mechanisms have been reported to have the capacity to target proteins to dense core secretory granules. Because proteins enter secretory granules with different efficiencies and because some of these proteins contain more than one granule-targeting motif, we have investigated whether compounding sorting signals could alter the efficiency of protein entry into secretory granules. In the current study we demonstrate that a paired basic cleavage site from human prorenin and an -helix-containing secretory granule-sorting signal from the prohormone convertase PC1/3 can synergize to increase granule-sorting efficiency not only when located on the same protein, but also when located on distinct proteins that associate in the secretory pathway.

Received for publication, July 29, 2004 , and in revised form, November 23, 2004.

^* This work was supported by operating Grant MOP-53177 from the Canadian Institutes for Health Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

To whom correspondence should be addressed: Clinical Research Inst. of Montreal, 110 Pine Ave. W., Montreal, QC H2W 1R7, Canada. Tel.: 514-987-5716; Fax: 514-987-5717; E-mail: reudelt{at}ircm.qc.ca.

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