Chromaffin granule membrane–F-actin interactions are calcium sensitive

Abstract

Exocytosis of neurotransmitters, hormones and other secretory products from many cell types is initiated by a rise in the intracellular free calcium ion concentration1. By analogy with excitation–contraction coupling in muscle2, calcium-triggered acto–myosin interactions have been postulated to push or pull the secretory granule to the plasma membrane1,3–6. Indeed, there have been several reports of actin interacting with membranes of secretory vesicles from the adrenal medulla (chromaffin granules)7–12. Using sedimentation techniques and a novel application13,14 of falling ball viscometry15,16 to measure actin binding to membranes, we show here that purified chromaffin granule membranes bind and cause large increases in the viscosity of F-actin. The actin-binding activity of the membranes is trypsin sensitive and thermolabile and interactions between membranes and actin are reversibly inhibited by raising the free calcium ion concentration, [Ca2+]free, above 10−7 M. We propose that regulation of actin–chromaffin granule membrane interactions may be critical for organelle movement to the plasma membrane during calcium-mediated exocytosis in the chromaffin cell.