A Lateral Cap model of microtubule dynamic instability

The co‐existence and interconversion of growing and shrinking microtubules have been termed ‘dynamic instability’, and have been directly observed to occur under a variety of conditions in vitro and in vivo. Previous modelling was based on the concept of an extensive, fluctuating cap of tubulin‐GTP to stabilise growing microtubules. A quantitative kinetic model is now presented in which only the terminal layer of the multi‐start helical microtubule lattice contains tubulin‐GTP molecules, comprising a ‘Lateral Cap’. In Monte Carlo numerical simulation, this model readily reproduces the decisive experimental evidence of microtubule dynamics, and predicts a co‐operative mechanism for microtubule transitions. The model also suggests how differing kinetic properties at opposite ends are the result of the intrinsic polarity of the microtubule lattice, reflecting the polarity of the tubutin α/β heterodimer.

[1]  M. Carlier,et al.  Stabilization of microtubules by inorganic phosphate and its structural analogues, the fluoride complexes of aluminum and beryllium. , 1988, Biochemistry.

[2]  T. L. Hill,et al.  Interference of GTP hydrolysis in the mechanism of microtubule assembly: an experimental study. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S Inoué,et al.  Asymmetric behavior of severed microtubule ends after ultraviolet- microbeam irradiation of individual microtubules in vitro , 1989, The Journal of cell biology.

[4]  E. Salmon,et al.  Dynamic instability of individual microtubules analyzed by video light microscopy: rate constants and transition frequencies , 1988, The Journal of cell biology.

[5]  H. Hotani,et al.  Visualization of the dynamic instability of individual microtubules by dark-field microscopy , 1986, Nature.

[6]  E D Salmon,et al.  Real-time observations of microtubule dynamic instability in living cells , 1988, The Journal of cell biology.

[7]  M. Kirschner,et al.  Dynamic instability of microtubule growth , 1984, Nature.

[8]  H. Erickson,et al.  GTP hydrolysis during microtubule assembly. , 1987, Biochemistry.

[9]  D. Pantaloni,et al.  Kinetic analysis of guanosine 5'-triphosphate hydrolysis associated with tubulin polymerization. , 1981, Biochemistry.

[10]  T. L. Hill,et al.  Monte Carlo study of the GTP cap in a five-start helix model of a microtubule. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Carlier,et al.  Mechanism of GTP hydrolysis in tubulin polymerization: characterization of the kinetic intermediate microtubule-GDP-Pi using phosphate analogues. , 1989, Biochemistry.

[12]  T. L. Hill,et al.  Steady-state theory of the interference of GTP hydrolysis in the mechanism of microtubule assembly. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Johnson Thermodynamics of the Polymerization of Protein , 1976 .

[14]  G. Borisy,et al.  Direct observation of microtubule dynamics in living cells , 1988, Nature.

[15]  J. McIntosh,et al.  Cytoskeleton: Dynamic microtubule dynamics , 1986, Nature.

[16]  M. Schilstra,et al.  On the relationship between nucleotide hydrolysis and microtubule assembly: studies with a GTP-regenerating system. , 1987, Biochemical and biophysical research communications.

[17]  F. Hallett,et al.  Dynamic instability of sheared microtubules observed by quasi-elastic light scattering. , 1988, Science.

[18]  M. Schilstra,et al.  A simple formulation of microtubule dynamics: quantitative implications of the dynamic instability of microtubule populations in vivo and in vitro. , 1989, Journal of cell science.

[19]  Fumio Oosawa,et al.  Thermodynamics of the polymerization of protein , 1975 .

[20]  E. Salmon,et al.  Dynamic instability of microtubules , 1987, BioEssays : news and reviews in molecular, cellular and developmental biology.

[21]  M. Kirschner,et al.  New features of microtubule behaviour observed in vivo , 1988, Nature.

[22]  M. Schilstra,et al.  The effect of podophyllotoxin on microtubule dynamics. , 1989, The Journal of biological chemistry.