Dynamics and mechanics of the microtubule plus end

Howard, Jonathon; Hyman, Anthony A.

doi:10.1038/nature01600

Cited by 657 publications

(530 citation statements)

References 74 publications

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“…These properties allow the overall radial array of MTs to be maintained while individual MTs turn over. Key players in these processes are members of the family of +TIPs (such as CLIP-170 and EB1) that localize preferentially at the plus end of growing MTs (Akhmanova and Hoogenraad, 2005;Howard and Hyman, 2003). These +TIPs can also mediate interactions with cortical or intracellular structures and have been implicated in signal transduction pathways that regulate MT organization and stability (Gundersen, 2002;.…”

Section: Introductionmentioning

confidence: 99%

Generation of noncentrosomal microtubule arrays

Bartolini

Gundersen

2006

Journal of Cell Science

226

215

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In most proliferating and migrating animal cells, the centrosome is the main site for microtubule (MT) nucleation and anchoring, leading to the formation of radial MT arrays in which MT minus ends are anchored at the centrosomes and plus ends extend to the cell periphery. By contrast, in most differentiated animal cell types, including muscle, epithelial and neuronal cells, as well as most fungi and vascular plant cells, MTs are arranged in noncentrosomal arrays that are non-radial. Recent studies suggest that these noncentrosomal MT arrays are generated by a three step process. The initial step involves formation of noncentrosomal MTs by distinct mechanisms depending on cell type: release from the centrosome, catalyzed nucleation at noncentrosomal sites or breakage of pre-existing MTs. The second step involves transport by MT motor proteins or treadmilling to sites of assembly. In the final step, the noncentrosomal MTs are rearranged into cell-type-specific arrays by bundling and/or capture at cortical sites, during which MTs acquire stability. Despite their relative stability, the final noncentrosomal MT arrays may still exhibit dynamic properties and in many cases can be remodeled.

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Section: Introductionmentioning

confidence: 99%

Generation of noncentrosomal microtubule arrays

Bartolini

Gundersen

2006

Journal of Cell Science

226

215

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“…Miscellaneous information about microtubules in C. elegans epithelia GENERAL BACKGROUND Microtubules are 25 nm wide hollow and rigid polymers assembled from a-tubulin and ß-tubulin heterodimers, which belong to guanosine-5'-triphosphate (GTP) hydrolase super-family. The binding of tubulin to GTP or GDP induces a conformational change that confers growth or shrinkage to microtubules (Brouhard, 2015;Howard and Hyman, 2003;Mitchison and Kirschner, 1984). In most eukaryotic cell types microtubules are assembled from 13 protofilaments, although C. elegans cells generally contain 11 protofilaments and their touch neurons 15 protofilaments.…”

Section: Noncentrosomal Microtubules Mediate Nuclear Positioningmentioning

confidence: 99%

Noncentrosomal microtubules in C. elegans epithelia

Quintin

Gally

Labouesse

2016

Genesis

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Summary:The microtubule cytoskeleton has a dual contribution to cell organization. First, microtubules help displace chromosomes and provide tracks for organelle transport. Second, microtubule rigidity confers specific mechanical properties to cells, which are crucial in cilia or mechanosensory structures. Here we review the recently uncovered organization and functions of noncentrosomal microtubules in C. elegans epithelia, focusing on how they contribute to nuclear positioning and protein transport. In addition, we describe recent data illustrating how the microtubule and actin cytoskeletons interact to achieve those functions. genesis 54:229-242, 2016. V C 2016 Wiley Periodicals, Inc.

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“…MT assembly consumes energy since tubulins bound to GTP are added to MT ends during polymerization. GTP is then hydrolyzed to GDP, and most of the MT, except its tip and possibly very small segments along the MT wall, is composed of tubulins bound to GDP [Howard and Hyman, 2003;Dimitrov et al, 2008;van der Vaart et al, 2009]. As a MT depolymerizes, the released tubulin dimers exchange their bound GDP for GTP.…”

Section: Views Articlementioning

confidence: 99%

Fueled by microtubules: Does tubulin dimer/polymer partitioning regulate intracellular metabolism?

et al. 2012

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Microtubules (MTs) or their subunits, tubulin dimers, interact with multiple components that contribute to intracellular metabolic pathways. MTs are required for insulin-dependent transport of glucose transporter 4 to the plasma membrane, they bind most glycolytic enzymes and are required for translation of the mRNA encoding hypoxia inducible factor-1a. Tubulin dimers bind the voltage-dependent anion channel of the mitochondrial outer membrane; this channel functions in metabolite transport in and out of mitochondria. We hypothesize that tubulin partitioning between dimer and polymer pools regulates multiple steps in metabolism, where metabolic output is greatest when both tubulin dimers and MT polymers are present and reduced by drug treatments that disrupt this normal balance. Experimental evidence from these drug-induced changes in tubulin dimer/polymer partitioning supports our model for several metabolic steps. Signal transduction pathways that stabilize or destabilize MTs can shift the normal ratio between unpolymerized and polymerized tubulin dimers, and one downstream consequence of this shift in tubulin partitioning could be a change in metabolic output. V C 2012 Wiley Periodicals, Inc Key Words: glycolysis, oxidative phosphorylation, glucose transport, voltage-dependent anion channel, tubulin IntroductionT he microtubule (MT) cytoskeleton has well-characterized roles in cell polarity, motility, mitosis, and vesicle traffic. The dynamic turnover of MTs is critical to most of these processes, allowing the cell to reorganize an array of MTs rapidly for specific functions. Here we posit an additional role for MTs in regulating metabolic processes and propose that metabolism is greatest when both MTs and their tubulin subunits are present in cells. Disruption of this normal balance, to either inhibit or promote MT polymerization, is expected to decrease metabolic output. Our hypothesis predicts that chemotherapies that stabilize or destabilize MTs will significantly impact metabolic pathways and reduce ATP levels. Importantly, even a small decrease in ATP production can slow cell proliferation. For example, a 19% decrease in ATP production was sufficient to induce senescence in mouse embryo fibroblasts [Kondoh et al., 2005], indicating that even a relatively small contribution of the MT cytoskeleton to metabolic output could have a significant impact on cell fate.The metabolic components and pathways we consider here include glucose transporters (GLUTs), glycolysis, the pentose phosphate pathway (PPP), and mitochondrial oxidative phosphorylation. Glucose enters cells through glucose transporters called GLUTs; the concentration of GLUTs at the plasma membrane can be regulated by insulin and requires trafficking of GLUT-containing vesicles along MTs to reach the plasma membrane. Within the cytoplasm, glucose is broken down to pyruvate during glycolysis, yielding ATP and NADH. Several intermediate products of glucose breakdown, including glucose-6-phosphate (G6P) and glyceraldehyde-3-phosphate (GAP), can also ...

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Dynamics and mechanics of the microtubule plus end

Cited by 657 publications

References 74 publications

Generation of noncentrosomal microtubule arrays

Generation of noncentrosomal microtubule arrays

Noncentrosomal microtubules in C. elegans epithelia

Fueled by microtubules: Does tubulin dimer/polymer partitioning regulate intracellular metabolism?

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