Hou Yanan, Ernst Stephen A, Lentz Stephen I, Williams John A
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Biochem Biophys Res Commun. 2016 Mar 18;471(4):610-5. doi: 10.1016/j.bbrc.2016.01.180. Epub 2016 Feb 2.
Small G protein Rab27B is expressed in various secretory cell types and plays a role in mediating secretion. In pancreatic acinar cells, Rab27B was found to be expressed on the zymogen granule membrane and by overexpression to regulate the secretion of zymogen granules. However, the effect of Rab27B deletion on the physiology of pancreatic acinar cells is unknown. In the current study, we utilized the Rab27B KO mouse model to better understand the role of Rab27B in the secretion of pancreatic acinar cells. Our data show that Rab27B deficiency had no obvious effects on the expression of major digestive enzymes and other closely related proteins, e.g. similar small G proteins, such as Rab3D and Rab27A, and putative downstream effectors. The overall morphology of acinar cells was not changed in the knockout pancreas. However, the size of zymogen granules was decreased in KO acinar cells, suggesting a role of Rab27B in regulating the maturation of secretory granules. The secretion of digestive enzymes was moderately decreased in KO acini, compared with the WT control. These data indicate that Rab27B is involved at a different steps of zymogen granule maturation and secretion, which is distinct from that of Rab3D.
小G蛋白Rab27B在多种分泌细胞类型中表达,并在介导分泌过程中发挥作用。在胰腺腺泡细胞中,发现Rab27B在酶原颗粒膜上表达,并且通过过表达来调节酶原颗粒的分泌。然而,Rab27B缺失对胰腺腺泡细胞生理学的影响尚不清楚。在当前研究中,我们利用Rab27B基因敲除小鼠模型来更好地了解Rab27B在胰腺腺泡细胞分泌中的作用。我们的数据表明,Rab27B缺陷对主要消化酶和其他密切相关蛋白的表达没有明显影响,例如类似的小G蛋白,如Rab3D和Rab27A,以及假定的下游效应器。敲除小鼠胰腺中腺泡细胞的整体形态没有改变。然而,敲除小鼠腺泡细胞中酶原颗粒的大小减小,表明Rab27B在调节分泌颗粒成熟中发挥作用。与野生型对照相比,敲除小鼠腺泡中消化酶的分泌适度减少。这些数据表明,Rab27B参与酶原颗粒成熟和分泌的不同步骤,这与Rab3D不同。