Regulated Secretion and Microfilaments

Page updated 13/11/02

Many cell types synthesize secretory products and store them in vesicles to be released upon stimulation with a relevant chemical or electrical signal.  This is known as stimulus-dependent, or regulated secretion. A dense network of actin filaments lies both between individual vesicles and between the vesicle population and the plasma-membrane and so there is a problem of how the cell is able to rapidly disassemble the microfilament network to permit the vesicles to fuse with each other and the plasma membrane during secretion (Puszkin et al, 1976; Meyer & Burger, 1979; Burgoyne & Cheek, 1987).

It has been suggested that the vesicles formed in the cell body travel to cellular extremities via molecular motors (e.g. kinesin, myosin1) and are prevented from diffusing from these sites by entanglement in a web of microfilaments.  Several studies have shown that secretory vesicles are surrounded by a dense web of actin filaments (Puszkin et al, 1976; Meyer & Burger, 1979) which also separates the vesicles from the plasma membrane.  It has been suggested that an actin filament severing protein “scinderin” is responsible for removing filaments underlying the plasma membrane (Trifaró et al, 1993), and while this may well be the case, it is likely that other severing proteins such as the ADF/Cofilins, are responsible for the rapid depolymerisation of the same filaments and in addition of filaments deeper within the cell, between the vesicles.  In a variety of cell types, exocytosis is potentiated by the disruption of microfilaments (Lelkes et al, 1986; Sontag et al, 1988; Muallem et al, 1995; Borovikov et al, 1995), and is inhibited by agents which stabilise microfilaments (Lelkes et al, 1986; Castellino et al, 1992).  The situation is more complex than this however as role of actin filaments in regulated secretion is not only inhibitory, Low concentrations of actin filament disrupting agents caused a stimulation of exocytosis when added to streptolysin-O permeabilised pancreatic acinar cells, yet higher concentrations of these agents inhibited secretion (Muallem et al, 1995).  This suggests that a minimal actin cytoskeleton is necessary for regulated exocytosis, in agreement with the finding that actin depolymerises from the cortex but re-polymerises deeper within the cell (Norman et al, 1994).  It is possible that the cofilins have properties which would allow them to sever filaments immediately on receipt of a secretory signal, and to allow re-polymerization of actin later in the secretion event.

 The role of Myosin II

(Spudich 1994)

References:-

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Spudich, A. (1994).  Myosin reorganization in activated RBL cells correlates temporally with stimulated secretion. Cell Mot.Cytoskel.  29  345-353.

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