Factors Regulating the Presence of Microtubules in Cells

When microtubules are required by a cell for a particular function, microtubules assemble in the appropriate region of the cell, with the necessary orientation. As microtubules are no longer needed, they depolymerize. The word, microtubules, describes a class of similar structures, formed of specific proteins called tubulins. In different microtubules, the tubulins are copolymerized with any of a variety of proteins collectively known as microtubule-associated proteins, or MAPs. Both the tubulins and at least some of the MAPs may be coded by more than a single gene; both tubulins and MAPs are modified in various ways after they are synthesized. Thus the determination of what sort of microtubule will be present a t a particular time in a particular cell depends, a t least in part, upon the synthesis and processing of a number of proteins. But the presence of the right proteins, while necessary, is not sufficient for assembly to occur. The assembly of many, if not all microtubules depends on the presence and orientation of microtubule organizing centers, which may include a centriole or analogous structure. I t is not clear what determines the length of a microtubule or what factors enable a cell to depolymerize its microtubules as required for normal cell function. In a living cell, one population of microtubules may be elongating a t the same time as another population is disassembling. The organizing principle for the conference on Dynamic Aspects of Microtubule Biology, and for this volume, is our understanding of the factors regulating the appearance and disappearance of microtubules in cells. All of the contributions to this conference deal with aspects of this fundamental feature of cell biology. As a point of departure for considering these problems, some basic features of what is known about factors regulating the presence of microtubules in a t least some cells will be reviewed in this chapter, which will serve as an introduction to the proceedings of the conference. What factors determine the presence of assembled microtubules in cells? Microtubule assembly may be seen to depend upon the size of the pool of subunits available for assembly; the microenvironment-the state of the cytoplasm; the presence of specific modulators of assembly such as MAPs, for example; and the mechanisms of the assembly and disassembly processes themselves. In simplest terms, microtubule assembly may be described by the following reaction:

[1]  M. Pittenger,et al.  Reconstruction of Tubulin Gene Regulation in Cultured Mammalian Cells a , 1986, Annals of the New York Academy of Sciences.

[2]  H. Detrich,et al.  Reversible dissociation of the alpha beta dimer of tubulin from bovine brain. , 1978, Biochemistry.

[3]  T. L. Hill,et al.  Bioenergetics and kinetics of microtubule and actin filament assembly-disassembly. , 1982, International review of cytology.

[4]  R. Margolis,et al.  Sliding of STOP Proteins on Microtubules: A Model System for Diffusion‐Dependent Microtubule Motility a , 1986, Annals of the New York Academy of Sciences.

[5]  Sheldon Penman,et al.  Mechanisms of regulating tubulin synthesis in cultured mammalian cells , 1979, Cell.

[6]  I. Rapin,et al.  Microtubule disarray in cortical dendrites and neurobehavioral failure. I. Golgi and electron microscopic studies. , 1982, Brain research.

[7]  H. Lassmann,et al.  Molecular Aspects of MAP‐1 and MAP‐2: Microheterogeneity, in Vitro Localization and Distribution in Neuronal and Nonneuronal Cells a , 1986, Annals of the New York Academy of Sciences.

[8]  Sumire V. Kobayashi,et al.  Association of Tau Protein with Microtubules in Living Cells , 1986, Annals of the New York Academy of Sciences.

[9]  A. Frankfurter,et al.  Differential Localization of MAP‐2 and Tau in Mammalian Neurons in Situ a , 1986, Annals of the New York Academy of Sciences.

[10]  D. Murphy,et al.  Tubulin Variants Exhibit Different Assembly Properties , 1986, Annals of the New York Academy of Sciences.

[11]  S. Farmer,et al.  Differential Expression of the β‐Tubulin Multigene Family during Rat Brain Development a , 1986 .

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

[13]  W. Griffin,et al.  Quantitation and in Situ Localization of Tubulin mRNA in the Mammalian Nervous System a , 1986, Annals of the New York Academy of Sciences.

[14]  James C. Lee,et al.  Biochemical and Chemical Properties of Tubulin Subspecies a , 1986, Annals of the New York Academy of Sciences.

[15]  T. Pollard,et al.  Interaction of Actin Filaments with Microtubules Is Mediated by Microtubule‐Associated Proteins and Regulated by Phosphorylation a , 1986, Annals of the New York Academy of Sciences.

[16]  M. Tsang,et al.  Genetic and Functional Analysis of Beta Tubulin in Aspergillus nidulans a , 1986, Annals of the New York Academy of Sciences.

[17]  J. Goldenring,et al.  Association of Calcium/Calmodulin‐Dependent Kinase with Cytoskeletal Preparations: Phosphorylation of Tubulin, Neurofilament, and Microtubule‐Associated Proteins a , 1986, Annals of the New York Academy of Sciences.

[18]  G. Bloom,et al.  Isolation of Mitotic Microtubule‐Associated Proteins from Sea Urchin Eggs a , 1986, Annals of the New York Academy of Sciences.

[19]  S. Brady,et al.  Axonal Transport of Microtubule Proteins: Cytotypic Variation of Tubulin and MAPs in Neurons a , 1986, Annals of the New York Academy of Sciences.

[20]  C. Silflow,et al.  Chlamydomonas reinhardtii Tubulin Gene Structure , 1986, Annals of the New York Academy of Sciences.

[21]  J. Olmsted,et al.  Distribution of MAP‐4 in Cells and in Adult and Developing Mouse Tissues a , 1986, Annals of the New York Academy of Sciences.

[22]  G. Gundersen,et al.  Distinct populations of microtubules: Tyrosinated and nontyrosinated alpha tubulin are distributed differently in vivo , 1984, Cell.

[23]  D. Pantaloni,et al.  Involvement of Guanosine Triphosphate (GTP) Hydrolysis in the Mechanism of Tubulin Polymerization: Regulation of Microtubule Dynamics at Steady State by a GTP Cap , 1986, Annals of the New York Academy of Sciences.

[24]  Robley C. Williams.  Interactions of Microtubules with Neuronal Intermediate Filaments in Vitro a , 1986, Annals of the New York Academy of Sciences.

[25]  J. Wehland,et al.  Contribution of Microtubules to Cellular Physiology: Microinjection of Well‐Characterized Monoclonal Antibodies into Cultured Cells , 1986, Annals of the New York Academy of Sciences.

[26]  J. Mazié,et al.  Tau Microheterogeneity: An Immunological Approach with Monoclonal Antibodies a , 1986, Annals of the New York Academy of Sciences.

[27]  R. Burgoyne,et al.  Immunocytochemical demonstration of alpha-tubulin modification during axonal maturation in the cerebellar cortex , 1984, The Journal of cell biology.

[28]  L. Wilson,et al.  Kinetics and Steady State Dynamics of Tubulin Addition and Loss at Opposite Microtubule Ends: The Mechanism of Action of Colchicine a , 1986, Annals of the New York Academy of Sciences.

[29]  G. Bloom,et al.  Differential Structure and Distribution of the High Molecular Weight Brain Microtubule‐Associated Proteins, MAP‐1 and MAP‐2 , 1986, Annals of the New York Academy of Sciences.

[30]  U Z Littauer,et al.  Isolation and Characterization of Two Rat Alpha‐Tubulin Isotypes a , 1986, Annals of the New York Academy of Sciences.

[31]  F. Maxfield,et al.  Calcium and Calmodulin in the Regulation of the Microtubular Cytoskeleton a , 1986, Annals of the New York Academy of Sciences.

[32]  I. Gozes,et al.  Multiple tubulin forms are expressed by a single neurone , 1981, Nature.

[33]  F. Solomon.  What Might MAPs Do? Results of an in Situ Analysis , 1986, Annals of the New York Academy of Sciences.

[34]  A. Matus,et al.  Microtubule‐Associated Proteins in the Developing Brain , 1986, Annals of the New York Academy of Sciences.