The nature and regulation of actin filament turnover in cells.
Actin filaments in mammalian cells form a number of different architectures in conjunction with a number of different actin-binding proteins. In motile cells these complex architectural arrangements of actin filaments and associated proteins continuously adjust their 3-dimensional organisation to modify the shape and behaviour of cells in response to external information. Microinjection experiments with fluorescently-labelled actin monomers suggest that there is a continual exchange of monomers between the actin filaments and a soluble pool such that individual monomers exist for only a few minutes within polymers. These data suggest that remodelling of the actin filament architectures occurs by the continuous assembly of new filaments which is balanced by the disassembly of obsolete structures. The mechanisms driving and regulating the assembly and disassembly cycle are not yet clearly understood. The properties of the actin assembly ATPase in vitro suggest that the intrinsic exchange of monomers between polymers and the monomer pool is driven by the stoichiometric ATP hydrolysis which is uncoupled from monomer addition and leads to both treadmilling and to the potential for mechanisms analogous to the dynamic instability models proposed for microtubules. Because of the relatively rapid rate of ATP hydrolysis by monomers in the filament (k = 0.05-0.02/s), it is assumed that most of the F-actin in cells is in its ADP form. ADP-F-actin binds inorganic phosphate with a Kd close to that of cytoplasmic concentrations to form an ADP.Pi-F-actin form which has different kinetic, structural and behavioural properties to ADP-F-actin.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheterline
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Department of Human Anatomy and Cell Biology, University of Liverpool, U.K.
Handel
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Molloy
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Hendry
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D000199:Actins / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*
D000199:Actins; D008840:Microfilament Proteins