Cytoskeletal coordination of pancreatic function
Tanzi, Jeffrey C.
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The pancreas gland is composed of both exocrine and endocrine components. The endocrine component regulates blood sugar levels and the exocrine component produces digestive enzymes that are secreted into the small intestine to aid in digestion. The pancreas must balance the production of new enzymes with the release of active enzymes. Enzyme production begins in the ER and undergoes modification in the golgi apparatus where inactive enzymes are packaged in vesicles. The vesicles dock with the plasma membrane and are secreted into the small intestine after food triggers the release of activating hormones. Although these mechanisms outlining both production and release are known, coordination between the two processes remains undetermined. The present project was developed on the hypothesis that the cytoskeleton contributes to the coordination between enzyme production and release. The cytoskeleton has historically been associated with maintaining cell structure and facilitating movement; however, recent studies have shown cytoskeletal elements attached to nonstructural proteins and signaling molecules. The present results show that ERK phosphorylation decreases when microtubules are depolymerized with cholchicine. However, inhibition of myosin ATPase activity by 2,3-butanedione monoxime (BDM) causes an increase in ERK phosphorylation and a decrease in secretion. Data with the myosin motor protein inhibitor ML-9 also showed an increase in ERK phosphorylation but a decrease when intracellular calcium was increased. The results support the requirement for the cytoskeleton system in pancreatic signalling and that the microfilaments are necessary for the coordination of production and exocytotic release.