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Molecular and Cellular Biology, September 2002, p. 6487-6497, Vol. 22, No. 18
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.18.6487-6497.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Rab3D Is Not Required for Exocrine Exocytosis but for Maintenance of Normally Sized Secretory Granules

Dietmar Riedel,1 Wolfram Antonin,1 Rafael Fernandez-Chacon,2 Guillermo Alvarez de Toledo,2 Tobias Jo,1 Martin Geppert,3,{dagger} Jack A. Valentijn,4 Karin Valentijn,5 James D. Jamieson,5 Thomas C. Südhof,6 and Reinhard Jahn1*

Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen,1 Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37073 Göttingen, Germany,3 Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain,2 Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510,5 Department of Biochemistry, Cell Biology and Histology, Faculty of Veterinary Medicine, University of Utrecht, 3584 CL Utrecht, The Netherlands,4 Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, Southwestern Medical Center, University of Texas, Dallas, Texas 753906

Received 19 February 2002/ Returned for modification 24 April 2002/ Accepted 12 June 2002

Rab3D, a member of the Rab3 subfamily of the Rab/ypt GTPases, is expressed on zymogen granules in the pancreas as well as on secretory vesicles in mast cells and in the parotid gland. To shed light on the function of Rab3D, we have generated Rab3D-deficient mice. These mice are viable and have no obvious phenotypic changes. Secretion of mast cells is normal as revealed by capacitance patch clamping. Furthermore, enzyme content and overall morphology are unchanged in pancreatic and parotid acinar cells of knockout mice. Both the exocrine pancreas and the parotid gland show normal release kinetics in response to secretagogue stimulation, suggesting that Rab3D is not involved in exocytosis. However, the size of secretory granules in both the exocrine pancreas and the parotid gland is significantly increased, with the volume being doubled. We conclude that Rab3D exerts its function during granule maturation, possibly by preventing homotypic fusion of secretory granules.


* Corresponding author. Mailing address: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Phone: 49-551 201 1634. Fax: 49-551 201 1639. E-mail: rjahn{at}gwdg.de.

{dagger} Present address: Pharmacia Corporation, Kalamazoo, MI 49007.


Molecular and Cellular Biology, September 2002, p. 6487-6497, Vol. 22, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.18.6487-6497.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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