Small G proteins as key regulators of pancreatic digestive enzyme secretion - PubMed (original) (raw)

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Small G proteins as key regulators of pancreatic digestive enzyme secretion

John A Williams et al. Am J Physiol Endocrinol Metab. 2009 Mar.

Abstract

Small GTP-binding (G) proteins act as molecular switches to regulate a number of cellular processes, including vesicular transport. Emerging evidence indicates that small G proteins regulate a number of steps in the secretion of pancreatic acinar cells. Diverse small G proteins have been localized at discrete compartments along the secretory pathway and particularly on the secretory granule. Rab3D, Rab27B, and Rap1 are present on the granule membrane and play a role in the steps leading up to exocytosis. Whether the function of these G proteins is simply to ensure appropriate targeting or if they are involved as regulatory molecules is discussed. Most evidence suggests that Rab3D and Rab27B play a role in tethering the secretory granule to its target membrane. Other Rabs have been identified on the secretory granule that are associated with different steps in the secretory pathway. The Rho family small G proteins RhoA and Rac1 also regulate secretion through remodeling of the actin cytoskeleton. Possible mechanisms for regulation of these G proteins and their effector molecules are considered.

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Figures

Fig. 1.

Fig. 1.

Small G proteins as regulators of the steps by which secretory proteins move through the secretory pathway from rough endoplasmic reticulum (RER) to enzyme release by exocytosis. TGN, trans-Golgi network. Small G proteins are listed in blue and shown next to steps where they have been identified. Other proteins identified on zymogen granules (ZGs), which may play a role in secretion, are listed in black. R_ight_: mature ZGs pass through the actin filaments of the terminal web with the aid of RhoA and Rac1, are attached to the membrane by tethering proteins, and then dock and fuse with the apical membrane to release their contents. These terminal steps involve the participation of SNARE proteins. At the time of fusion, the granules also become coated with actin, and at least some of the G proteins are released.

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