The Role of Microtubules in Secretion

Abstract

Microtubules have been implicated in the movement of secretory granules to the cell membrane in a variety of both exocrine and endocrine cells. A range of roles, from provision of the motive force to preventing presecretory movement, have been attributed to these organelles. An in vitro model system to investigate the interaction between isolated exocrine pancreatic zymogen granules and brain microtubules has been devised. This system has been studied by electron microscopy, colchicine binding assay for the microtubule protein tubulin and radioimmunoassay. These assays for microtubule proteins have been performed on mouse pancreas homogenates to test whether a correlation exists between the assembly of microtubules in vivo and secretion in response to a known secretagogue, Pilocarpine. The in vitro model .demonstrated an interaction between microtubules and the membrane of zymogen granules. Attachment was produced by the micro-tubule side arms and possibly a membrane component. This morphological observation was confirmed by the colchicine binding assay which showed that zymogen granules removed tubulin as assembled microtubules from solution upon sedimentation. The investigation of the pancreas microtubule—free tubulin equilibrium during Pilocarpine-induced secretion showed that secretion was accompanied by a reduction in the assembled microtubules. A concomitant increase in the measurable free tubulin was initially produced followed by a rapid decrease. These findings provide evidence for an important role for microtubules in exocrine pancreas secretion. Secretory zymogen granules appear to bind specifically to microtubules and Pilocarpine-induced secretion seems to induce microtubule disassembly allowing granules to migrate to the site of release under the influence of an unknown mechanism.