Dynamics of the microtubule oscillator: role of nucleotides and tubulin-MAP interactions.
Microtubules can be induced to perform synchronous and periodic cycles of assembly and disassembly at constant temperature. The process depends on GTP hydrolysis. Time-resolved X-ray scattering using synchrotron radiation shows a cyclic interconversion of tubulin subunits, microtubules and oligomers (= short protofilament fragments). Oscillations are correlated with conditions that stabilize polymers and destabilize oligomers, and others of opposite effect. Microtubule stabilizers include GTP, Mg2+ or microtubule-associated proteins (MAPs), destabilizers include GDP or elevated ionic strength. K+ at intracellular concentrations noticeably increases the stability of tubulin-MAP oligomers, in contrast to Na+. ATP and the non-hydrolyzable analogue AMP-PNP enhance oscillations by mechanisms that are not directly linked to the role of nucleotide hydrolysis in assembly. We propose a mechanism of oscillations that include oligomers as microtubule disassembly products which transiently lock the protein in an unpolymerizable state; this may point to a role of oligomers in controlling microtubule assembly cycles in cells.
Mandelkow
E M
EM
Max-Planck-Unit for Structural Molecular Biology, Hamburg, FRG.
Lange
G
G
Jagla
A
A
Spann
U
U
Mandelkow
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D012265:Ribonucleotides / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D014961:X-Ray Diffraction
D008869:Microtubule-Associated Proteins; D012265:Ribonucleotides; D014404:Tubulin; D000266:Adenylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate