Riedel Dietmar, Antonin Wolfram, Fernandez-Chacon Rafael, Alvarez de Toledo Guillermo, Jo Tobias, Geppert Martin, Valentijn Jack A, Valentijn Karin, Jamieson James D, Südhof Thomas C, Jahn Reinhard
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Mol Cell Biol. 2002 Sep;22(18):6487-97. doi: 10.1128/MCB.22.18.6487-6497.2002.
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.
Rab3D是Rab/ypt GTP酶家族Rab3亚家族的成员之一，在胰腺的酶原颗粒以及肥大细胞和腮腺的分泌囊泡上表达。为了阐明Rab3D的功能，我们培育出了Rab3D基因缺陷型小鼠。这些小鼠能够存活，且没有明显的表型变化。通过电容膜片钳检测发现，肥大细胞的分泌正常。此外，基因敲除小鼠的胰腺和腮腺腺泡细胞中的酶含量和整体形态均未改变。外分泌胰腺和腮腺在促分泌素刺激下均表现出正常的释放动力学，这表明Rab3D不参与胞吐作用。然而，外分泌胰腺和腮腺中分泌颗粒的大小均显著增加，体积增大了一倍。我们得出结论，Rab3D可能通过阻止分泌颗粒的同型融合在颗粒成熟过程中发挥作用。
