scholarly journals Microtubule dynamic instability: A new model with coupled GTP hydrolysis and multistep catastrophe

BioEssays ◽  
2013 ◽  
Vol 35 (5) ◽  
pp. 452-461 ◽  
Author(s):  
Hugo Bowne‐Anderson ◽  
Marija Zanic ◽  
Monika Kauer ◽  
Jonathon Howard
Keyword(s):  
Dynamic Instability ◽  
Microtubule Dynamic ◽  
Gtp Hydrolysis ◽  
New Model

Analysis of the Mechanism of Microtubule Dynamic Instability Using a UV Microbeam to Sever Elongating Microtubules

1988 ◽  
Vol 46 ◽  
pp. 122-123
Author(s):  
R.A Walker ◽  
S. Inoue ◽  
E.D. Salmon
Keyword(s):  
Dynamic Instability ◽  
Microtubule Dynamic ◽  
Gtp Hydrolysis ◽  
Abrupt Transition ◽  
Microtubule Associated Proteins ◽  
Asymmetrical Structure ◽  
Associated Proteins

Microtubules polymerized in vitro from tubulin purified free of microtubule-associated proteins exhibit dynamic instability (1,2,3). Free microtubule ends exist in persistent phases of elongation or rapid shortening with infrequent, but, abrupt transitions between these phases. The abrupt transition from elongation to rapid shortening is termed catastrophe and the abrupt transition from rapid shortening to elongation is termed rescue. A microtubule is an asymmetrical structure. The plus end grows faster than the minus end. The frequency of catastrophe of the plus end is somewhat greater than the minus end, while the frequency of rescue of the plus end in much lower than for the minus end (4).The mechanism of catastrophe is controversial, but for both the plus and minus microtubule ends, catastrophe is thought to be dependent on GTP hydrolysis. Microtubule elongation occurs by the association of tubulin-GTP subunits to the growing end. Sometime after incorporation into an elongating microtubule end, the GTP is hydrolyzed to GDP, yielding a core of tubulin-GDP capped by tubulin-GTP (“GTP-cap”).

Mathematical modeling of microtubule dynamic instability: new insight into the link between gtp-hydrolysis and microtubule aging

2018 ◽  
Vol 52 (6) ◽  
pp. 2433-2456 ◽  
Author(s):  
Ayuna Barlukova ◽  
Diana White ◽  
Gérard Henry ◽  
Stéphane Honoré ◽  
Florence Hubert
Keyword(s):  
Dynamic Instability ◽  
Dynamic Properties ◽  
Model Parameters ◽  
Microtubule Dynamic ◽  
Gtp Hydrolysis ◽  
Unique Type ◽  
Microtubule Targeting Agents ◽  
Age Dependent ◽  
Type Of Behavior ◽  
Insight Into

Microtubules (MTs) are protein polymers that exhibit a unique type of behavior referred to as dynamic instability. That is, they undergo periods of growth (through the addition of GTP-tubulin) and shortening (through the subtraction of GDP-tubulin). Shortening events are very fast, where this transition is referred to as a catastrophe. There are many processes that regulate MT dynamic instability, however, recent experiments show that MT dynamics may be highly regulated by a MTs age, where young MTs are less likely to undergo shortening events than older ones. In this paper, we develop a novel modeling approach to describe how the age of a MT affects its dynamic properties. In particular, we extend on a previously developed model that describes MT dynamics, by proposing a new concept for GTP-tubulin hydrolysis (the process by which newly incorporated GTP-tubulin is hydrolyzed to lower energy GDP-tubulin). In particular, we assume that hydrolysis is mainly vectorial, age-dependent and delayed according to the GTP-tubulin incorporation into the MT. Through numerical simulation, we are able to show how MT age affects certain properties that define MT dynamics. For example, simulations illustrate how the aging process leads to an increase in the rate of GTP-tubulin hydrolysis for older MTs, as well as increases in catastrophe frequency. Also, since it has been found that MT dynamic instability is affected by chemotherapy microtubule-targeting agents (MTAs), we highlight the fact that our model can be used to investigate the action of MTAs on MT dynamics by varying certain model parameters.

scholarly journals Abstract P-33: Structural Basis for the Growing Microtubule End Recognition by End Binding Proteins

2021 ◽  
Vol 11 (Suppl_1) ◽  
pp. S26-S26
Author(s):  
Alena Korshunova
Keyword(s):  
Amino Acids ◽  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Molecular Mechanism ◽  
Binding Proteins ◽  
Dynamic Instability ◽  
3D Structure ◽  
Structural Basis ◽  
Microtubule Dynamic ◽  
Gtp Hydrolysis

Background: Eukaryotic end binding proteins (EBs) can follow the growing microtubule end. EBs play a crucial role in microtubule dynamic instability and promote simultaneously growth rate and catastrophe frequency. It makes EB-like proteins perspective drag targets for a wide number of diseases. But the molecular mechanism of tip tracking by EB-like proteins remains unknown. Studies of mutants have revealed that the conservative amino acid Q102 (numbering relative to the human EB1 protein) plays a key role in the recognition of the growing microtubule end. However, the 3D structure studies revealed that this amino acid has no bonds with tubulin. In this work, we performed structural and phylogenetic analysis of EBs proteins to identify a possible molecular mechanism behind the plus end tracking. Methods: UCSF Chimera10 was used for structural analysis. Phylogenetic analysis was performed with MEGA X software. 3D structures of EBs and microtubules with different states of GTP hydrolysis were used (pdb 3JAK, 3JAS, 3JAT, 3JAW, 3JAL, 3JAR, 6DPU, 6DPV, 6DPW). Results: We have shown that two conservative amino acids (K100, E106) should play an important role in the recognition of the microtubule plus end in addition to Q102. It was concluded that these amino acids together form the plus-end «navigation site» of EBs. Analysis of possible interaction of the «navigation site» amino acids with microtubules in different conformational states suggested that the main mechanism of growing microtubule end recognition is not due to an affinity increase for a certain state of tubulin in microtubules at their end, but it due to a significant affinity decrease in other parts of the microtubule as a result of steric clashes. Conclusion: Thus, the results of the analysis suggested the possible molecular mechanism that provides the tip tracking by EB-like proteins and allowed us to identify the key amino acids of this mechanism.

scholarly journals A mutation uncouples the tubulin conformational and GTPase cycles, revealing allosteric control of microtubule dynamics

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Elisabeth A Geyer ◽  
Alexander Burns ◽  
Beth A Lalonde ◽  
Xuecheng Ye ◽  
Felipe-Andres Piedra ◽  
...  
Keyword(s):  
Conformational Change ◽  
Dynamic Instability ◽  
Dynamic Properties ◽  
Microtubule Dynamics ◽  
Gtpase Activity ◽  
Microtubule Dynamic ◽  
Gtp Hydrolysis ◽  
Allosteric Control

Microtubule dynamic instability depends on the GTPase activity of the polymerizing αβ-tubulin subunits, which cycle through at least three distinct conformations as they move into and out of microtubules. How this conformational cycle contributes to microtubule growing, shrinking, and switching remains unknown. Here, we report that a buried mutation in αβ-tubulin yields microtubules with dramatically reduced shrinking rate and catastrophe frequency. The mutation causes these effects by suppressing a conformational change that normally occurs in response to GTP hydrolysis in the lattice, without detectably changing the conformation of unpolymerized αβ-tubulin. Thus, the mutation weakens the coupling between the conformational and GTPase cycles of αβ-tubulin. By showing that the mutation predominantly affects post-GTPase conformational and dynamic properties of microtubules, our data reveal that the strength of the allosteric response to GDP in the lattice dictates the frequency of catastrophe and the severity of rapid shrinking.

scholarly journals Temperature-jump studies of microtubule dynamic instability.

1988 ◽  
Vol 263 (21) ◽  
pp. 10344-10352
Author(s):  
M Caplow ◽  
J Shanks ◽  
R L Ruhlen
Keyword(s):  
Temperature Jump ◽  
Dynamic Instability ◽  
Microtubule Dynamic

scholarly journals Motile kinetochores and polar ejection forces dictate chromosome position on the vertebrate mitotic spindle

1994 ◽  
Vol 124 (3) ◽  
pp. 223-233 ◽  
Author(s):  
CL Rieder ◽  
ED Salmon
Keyword(s):  
Mitotic Spindle ◽  
Constant Velocity ◽  
Molecular Mechanisms ◽  
Dynamic Instability ◽  
Microtubule Dynamic ◽  
Pole Motion ◽  
Microtubule Motors ◽  
Chromosome Position ◽  
Pulling Forces

We argue that hypotheses for how chromosomes achieve a metaphase alignment, that are based solely on a tug-of-war between poleward pulling forces produced along the length of opposing kinetochore fibers, are no longer tenable for vertebrates. Instead, kinetochores move themselves and their attached chromosomes, poleward and away from the pole, on the ends of relatively stationary but shortening/elongating kinetochore fiber microtubules. Kinetochores are also "smart" in that they switch between persistent constant-velocity phases of poleward and away from the pole motion, both autonomously and in response to information within the spindle. Several molecular mechanisms may contribute to this directional instability including kinetochore-associated microtubule motors and kinetochore microtubule dynamic instability. The control of kinetochore directional instability, to allow for congression and anaphase, is likely mediated by a vectorial mechanism whose magnitude and orientation depend on the density and orientation or growth of polar microtubules. Polar microtubule arrays have been shown to resist chromosome poleward motion and to push chromosomes away from the pole. These "polar ejection forces" appear to play a key role in regulating kinetochore directional instability, and hence, positions achieved by chromosomes on the spindle.

scholarly journals Regulation of Mitotic Microtubule Dynamic Instability in Monopolar Spindles by Bundling and Kinetochore Attachment

2017 ◽  
Vol 31 (S1) ◽  
Author(s):  
Zachary R Gergely ◽  
Patrick J Flynn ◽  
Salvador Montes ◽  
J. Richard McIntosh ◽  
M. D. Betterton
Keyword(s):  
Dynamic Instability ◽  
Microtubule Dynamic

scholarly journals Inhibition of HDAC6 Deacetylase Activity Increases Its Binding with Microtubules and Suppresses Microtubule Dynamic Instability in MCF-7 Cells

2013 ◽  
Vol 288 (31) ◽  
pp. 22516-22526 ◽  
Author(s):  
Jayant Asthana ◽  
Sonia Kapoor ◽  
Renu Mohan ◽  
Dulal Panda
Keyword(s):  
Dynamic Instability ◽  
Microtubule Dynamic ◽  
Mcf 7
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