Molecular mechanism of histamine release: the role of intermediate filaments and membrane skeletons.

It has been recognized that cytoskeletons play some important roles in the histamine release from mast cells. We previously reported the role of microfilaments and microtubules in the histamine release from mast cells, and in the present study, the roles of intermediate filaments and membrane skeletons were investigated. When permeabilized mast cells were stimulated with Ca2+, a translocation of protein kinase C from cytosol to the membrane fraction was observed. This lead to the phosphorylation of vimentin, one of the component proteins of the intermediate filaments. Phosphorylation of vimentin induced disruption of intermediate filaments and resulted in an increase in the mobility of granules. This may be favorable for the initiation of degranulation. In the membrane skeletons of rat mast cells, alpha- and beta-fodrin, ankyrin and actin were found. Changes in the distribution of the fodrin network were elicited by antigen-antibody reaction. It is suggested that membrane skeletons may act as a barrier between the plasma membrane and the granule membrane and that the changes in the distribution of membrane skeletons may facilitate the initiation of the fusion of the plasma membrane and granular membrane.