Microtubules grow and shorten at intrinsically variable rates.

Gildersleeve, Rachel; Cross, Alan R.; Cullen, Katherine; Fagen, A P; Williams, Robley C.

doi:10.1016/s0021-9258(18)42399-x

Cited by 116 publications

(64 citation statements)

References 60 publications

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“…fIRth = ASotherh5.6 (Spolar and Record, 1994). Horio and Hotani, 1986;Gildersleeve et al, 1992). It is also 1992).…”

Section: Discussionmentioning

confidence: 97%

“…This is of interest because Chretien et al (1995) have proposed a linkage between GTP hydrolysis and the closure of sheet-like extension off growing microtubules into a microtubule cylinder. They suggest that variable rates of closure may regulate the variable rate of microtubule growth observed by video-enhanced DIC (differential interference contrast microscopy) (Gildersleeve et al, 1992). Although the results of Chretien et al (1995) are based on kinetic experiments, they suggest that microtubules grown with a nonhydrolyzable analog, GMPCPP, may have a greater tendency to form sheets than microtubules.…”

Section: Enthalpy-entropy Compensation Analysismentioning

confidence: 99%

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Thermodynamic and structural analysis of microtubule assembly: the role of GTP hydrolysis

Vulevic¹,

Correia²

1997

Biophysical Journal

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Different models have been proposed that link the tubulin heterodimer nucleotide content and the role of GTP hydrolysis with microtubule assembly and dynamics. Here we compare the thermodynamics of microtubule assembly as a function of nucleotide content by van't Hoff analysis. The thermodynamic parameters of tubulin assembly in 30-100 mM piperazine-N,N'-bis(2-ethanesulfonic acid), 1 mM MgSO4, 2 mM EGTA, pH 6.9, in the presence of a weakly hydrolyzable analog, GMPCPP, the dinucleotide analog GMPCP plus 2 M glycerol, and GTP plus 2 M glycerol were obtained together with data for taxol-GTP/GDP tubulin assembly (GMPCPP and GMPCP are the GTP and GDP nucleotide analogs where the alpha beta oxygen has been replaced by a methylene, -CH2-). All of the processes studied are characterized by a positive enthalpy, a positive entropy, and a large, negative heat capacity change. GMPCP-induced assembly has the largest negative heat capacity change and GMPCPP has the second largest, whereas GTP/2 M glycerol- and taxol-induced assembly have more positive values, respectively. A large, negative heat capacity is most consistent with the burial of water-accessible hydrophobic surface area, which gives rise to the release of bound water. The heat capacity changes observed with GTP/2 M glycerol-induced and with taxol-induced assembly are very similar, -790 +/- 190 cal/mol/k, and correspond to the burial of 3330 +/- 820 A2 of nonpolar surface area. This value is shown to be very similar to an estimate of the buried nonpolar surface in a reconstructed microtubule lattice. Polymerization data from GMPCP- and GMPCPP-induced assembly are consistent with buried nonpolar surface areas that are 3 and 6 times larger. A linear enthalpy-entropy and enthalpy-free energy plot for tubulin polymerization reactions verifies that enthalpy-entropy compensation for this system is based upon true biochemical correlation, most likely corresponding to a dominant hydrophobic effect. Entropy analysis suggests that assembly with GTP/2 M glycerol and with taxol is consistent with conformational rearrangements in 3-6% of the total amino acids in the heterodimer. In addition, taxol binding contributes to the thermodynamics of the overall process by reducing the delta H degree and delta S degree for microtubule assembly. In the presence of GMPCPP or GMPCP, tubulin subunits associate with extensive conformational rearrangement, corresponding to 10% and 26% of the total amino acids in the heterodimer, respectively, which gives rise to a large loss of configurational entropy. An alternative, and probably preferable, interpretation of these data is that, especially with GMPCP-tubulin, additional isomerization or protonation events are induced by the presence of the methylene moiety and linked to microtubule assembly. Structural analysis shows that GTP hydrolysis is not required for sheet closure into a microtubule cylinder, but only increases the probability of this event occurring. Sheet extensions and sheet polymers appear to have a similar average length under var...

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“…fIRth = ASotherh5.6 (Spolar and Record, 1994). Horio and Hotani, 1986;Gildersleeve et al, 1992). It is also 1992).…”

Section: Discussionmentioning

confidence: 97%

Section: Enthalpy-entropy Compensation Analysismentioning

confidence: 99%

Thermodynamic and structural analysis of microtubule assembly: the role of GTP hydrolysis

Vulevic¹,

Correia²

1997

Biophysical Journal

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“…For the work presented here, it is important to recognize that the relevant observations are the behaviors of the systems at different scales and the concurrence (or disagreement) between the values of CC that result from various definitions or measurement approaches; the specific numerical CC values observed are simply outcomes of the particular input kinetic rate constants used and so are not by themselves significant. This situation is analogous to physical MTs, where DI parameters and CC values depend on the protein sequences, temperatures, and buffer conditions used (e.g., Williams et al, 1985;Gildersleeve et al, 1992;Fygenson et al, 1994;Hussmann et al, 2016;Schummel et al, 2017).…”

Section: Approach To Understanding the Relationship Between Microtubule Behaviors And Critical Concentrationsmentioning

confidence: 99%

Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis

Jonasson

Mauro

et al. 2020

MBoC

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“…MT dynamic instability has the following parameters: MT polymerization (growth) and depolymerization (shrinkage, shortening) rates, catastrophe (transition from polymerization to depolymerization) and rescue (transition from depolymerization to polymerization) frequencies, as well as pauses-states when MTs are not polymerized or depolymerized [12]. All parameters are finely regulated in a cell; the polymerization and depolymerization rates of individual MT can vary significantly both in cell and in different types of cells [13][14][15].…”

Section: Microtubules (Mts) and Their Properties Necessary For The Neuron's Development And Functioningmentioning

confidence: 99%

Huntington’s Disease—An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components

Taran

Shuvalova

Lagarkova

et al. 2020

Cells

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Huntington’s disease is a severe and currently incurable neurodegenerative disease. An autosomal dominant mutation in the Huntingtin gene (HTT) causes an increase in the polyglutamine fragment length at the protein N-terminus. The consequence of the mutation is the death of neurons, mostly striatal neurons, leading to the occurrence of a complex of motor, cognitive and emotional-volitional personality sphere disorders in carriers. Despite intensive studies, the functions of both mutant and wild-type huntingtin remain poorly understood. Surprisingly, there is the selective effect of the mutant form of HTT even on nervous tissue, whereas the protein is expressed ubiquitously. Huntingtin plays a role in cell physiology and affects cell transport, endocytosis, protein degradation and other cellular and molecular processes. Our experimental data mining let us conclude that a significant part of the Huntingtin-involved cellular processes is mediated by microtubules and other cytoskeletal cell structures. The review attempts to look at unresolved issues in the study of the huntingtin and its mutant form, including their functions affecting microtubules and other components of the cell cytoskeleton.

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Microtubules grow and shorten at intrinsically variable rates.

Cited by 116 publications

References 60 publications

Thermodynamic and structural analysis of microtubule assembly: the role of GTP hydrolysis

Thermodynamic and structural analysis of microtubule assembly: the role of GTP hydrolysis

Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis

Huntington’s Disease—An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components

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