Rab3D is not required for exocrine exocytosis but for maintenance of normally sized secretory granules.
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.
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Dietmar
D
Riedel
Wolfram
W
Antonin
Rafael
R
Fernandez-Chacon
Guillermo
G
Alvarez de Toledo
Tobias
T
Jo
Martin
M
Geppert
Jack A
JA
Valentijn
Karin
K
Valentijn
James D
JD
Jamieson
Thomas C
TC
Südhof
Reinhard
R
Jahn
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005089:Exocytosis; D005091:Exons; D007700:Kinetics; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010179:Pancreas / Q000502:physiology; D010306:Parotid Gland / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D010641:Phenotype; D020033:Protein Isoforms / Q000502:physiology; D022142:Secretory Vesicles / Q000648:ultrastructure*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D020033:Protein Isoforms; D002217:Carbachol; D000681:Amylases; C116711:Rab3d protein, mouse; D020692:rab3 GTP-Binding Proteins