Nucleotide hydrolysis in cytoskeletal assembly.
Two major polymers of the cytoskeleton, actin filaments and microtubules, are assembled with expenditure of energy: the ATP/GTP tightly bound to actin/tubulin is irreversibly hydrolyzed to ADP/GTP during the assembly process, and liberation of Pi in the medium occurs subsequent to the incorporation of subunits in the polymer. Pi release acts as a switch, causing the destabilization of protein-protein interactions in the polymer, therefore regulating the dynamics of these fibres. An understanding of this regulation in vivo requires that progress be made in four areas: the chemistry of the NTPase reaction; the structure of the intermediates in nucleotide hydrolysis and the nature of the conformational switch; the regulation of parameters involved in dynamic instability of microtubules; and the possible involvement of nucleotide hydrolysis in the macroscopic organization of these polymers in highly concentrated solutions, compared with the simple case of a equilibrium polymers. Progress made along these lines will define trends for future investigation.
Carlier
M F
MF
Laboratoire d'Enzymologie, CNRS, Gif-sur-Yvette, France.
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D008870:Microtubules / Q000378:metabolism; D008968:Molecular Conformation
D000199:Actins; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate