Microtubule composition: Cryptography of dynamic polymers

Bloom, Kerry

doi:10.1073/pnas.0401266101

Cited by 12 publications

(14 citation statements)

References 26 publications

(26 reference statements)

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“…More broadly, the proportion of stable vs dynamic MTs tends to increase and the tubulin isotype expression profile changes during cell differentiation. One exciting possibility is that the extensive tubulin diversity represents a complex code that can be deciphered and acted upon by interacting proteins [17; 20; 21]. …”

Section: Tubulin Isotypes and Functional Significance: First Hints Ofmentioning

confidence: 99%

Tubulin proteomics: Towards breaking the code

Verdier-Pinard

Pasquier

Xiao

et al. 2009

Analytical Biochemistry

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Since the discovery of tubulin as the major component of microtubules over 40 years ago, its diversity of forms has raised a continuum of fundamental questions about its regulation and functions in a variety of organisms across phyla. Its high abundance in the brain or in specialized organelles such as cilia has allowed early characterization of this important target for anticancer drugs. However, it was only when matrix-assisted laser desorption ionization and electrospray ionization mass spectrometry technologies became available in the late 1980's that the full complexity of tubulin expression patterns became more obvious. This contributed in a major way to the idea that due to increasing and conserved tubulin heterogeneity during evolution, a tubulin code read by microtubule associated proteins might exist and be of functional significance. We review here the merging of recent genetic and cell biology studies with proteomics to decipher this code and illustrate some of the tubulin proteomic approaches with new data generated in our laboratories.

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Section: Tubulin Isotypes and Functional Significance: First Hints Ofmentioning

confidence: 99%

Tubulin proteomics: Towards breaking the code

Verdier-Pinard

Pasquier

Xiao

et al. 2009

Analytical Biochemistry

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“…Tubulins that comprise microtubules become posttranslationally modified, and this modification highly correlates with the dynamics of microtubules. One of the best characterized modifications of tubulin is acetylation at lysine 40 of ␣-tubulin, which is considered to be a marker of stabilized microtubules (Bloom, 2004). We therefore examined effects of APC2 overexpression on the stability of microtubules using an antibody against acetylated ␣-tubulin.…”

Section: Apc2 Stabilizes Microtubulesmentioning

confidence: 99%

APC2 Plays an Essential Role in Axonal Projections through the Regulation of Microtubule Stability

Shintani¹,

Ihara²,

Tani³

et al. 2009

J. Neurosci.

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Growth cones at the tip of growing axons are key cellular structures that detect guidance cues and mediate axonal growth. An increasing number of studies have suggested that the dynamic regulation of microtubules in the growth cone plays an essential role in growth cone steering. The dynamic properties of microtubules are considered to be regulated by variegated cellular factors but, in particular, through microtubule-interacting proteins. Here, we examined the functional role of adenomatous polyposis coli-like molecule 2 (APC2) in the development of axonal projections by using the chick retinotectal topographic projection system. APC2 is preferentially expressed in the nervous system from early developmental stages through to adulthood. Immunohistochemical analysis revealed that APC2 is distributed along microtubules in growth cones as well as axon shafts of retinal axons. Overexpression of APC2 in cultured cells induced the stabilization of microtubules, whereas the knockdown of APC2 in chick retinas with specific short hairpin RNA reduced the stability of microtubules in retinal axons. APC2 knockdown retinal axons showed abnormal growth attributable to a reduced response to ephrin-A2 in vitro. Furthermore, they showed drastic alterations in retinotectal projections without making clear target zones in the tectum in vivo. These results suggest that APC2 plays a critical role in the development of the nervous system through the regulation of microtubule stability.

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“…Microtubules are conserved structures that are primarily composed of tubulin, and a dynamic equilibrium exists between free tubulin and polymerized tubulin [5, 6]. Microtubules support cellular architecture, plasma membranes, myofibrils and other cellular organelles via their filamentous network and provide pathways for transporting mitochondria, endoplasmic reticulum and other membranous organelles throughout the cell [7].…”

Section: Introductionmentioning

confidence: 99%

Taxol, a microtubule stabilizer, prevents ischemic ventricular arrhythmias in rats

Xiao

Cao

Liang

et al. 2010

Journal of Cellular and Molecular Medicine

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Microtubule integrity is important in cardio-protection, and microtubule disruption has been implicated in the response to ischemia in cardiac myocytes. However, the effects of Taxol, a common microtubule stabilizer, are still unknown in ischemic ventricular arrhythmias. The arrhythmia model was established in isolated rat hearts by regional ischemia, and myocardial infarction model by ischemia/reperfusion. Microtubule structure was immunohistochemically measured. The potential mechanisms were studied by measuring reactive oxygen species (ROS), activities of oxidative enzymes, intracellular calcium concentration ([Ca2+]i) and Ca2+ transients by using fluorometric determination, spectrophotometric assays and Fura-2-AM and Fluo-3-AM, respectively. The expression and activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) was also examined using real-time polymerase chain reaction, Western blot and pyruvate/Nicotinamide adenine dinucleotide-coupled reaction. Our data showed that Taxol (0.1, 0.3 and 1 μM) effectively reduced the number of ventricular premature beats and the incidence and duration of ventricular tachycardia. The infarct size was also significantly reduced by Taxol (1 μM). At the same time, Taxol preserved the microtubule structure, increased the activity of mitochondrial electron transport chain complexes I and III, reduced ROS levels, decreased the rise in [Ca2+]i and preserved the amplitude and decay times of Ca2+ transients during ischemia. In addition, SERCA2a activity was preserved by Taxol during ischemia. In summary, Taxol prevents ischemic ventricular arrhythmias likely through ameliorating abnormal calcium homeostasis and decreasing the level of ROS. This study presents evidence that Taxol may be a potential novel therapy for ischemic ventricular arrhythmias.

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Microtubule composition: Cryptography of dynamic polymers

Cited by 12 publications

References 26 publications

Tubulin proteomics: Towards breaking the code

Tubulin proteomics: Towards breaking the code

APC2 Plays an Essential Role in Axonal Projections through the Regulation of Microtubule Stability

Taxol, a microtubule stabilizer, prevents ischemic ventricular arrhythmias in rats

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