γ-Tubulin complexes in microtubule nucleation and beyond

Oakley, Berl R; Paolillo, Vitoria; Zheng, Yixian

doi:10.1091/mbc.e14-11-1514

Cited by 115 publications

(102 citation statements)

References 65 publications

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“…A significant reduction in MEK1/2 suggests further compromise in effector NK cell function. Following the activation of triggers, a signaling cascade via sequential phosphorylation of MAPK, MEK, and ERK results in the lytic granule polarization mediated by TUBB,45 which regulates the reorientation of the microtubule and microtubule-organizing centre (MTOC) toward target cells to release perforin and granzymes. Activation of ERK1/2 facilitates polarization of cytotoxic granules toward the MTOC 46,47.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Chacko

Staines

Johnston

et al. 2016

Gene�Regul Syst Bio

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BACKGROUNDThe etiology and pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are unknown. However, natural killer (NK) cell dysfunction, in particular reduced NK cytotoxic activity, is a consistent finding in CFS/ME patients. Previous research has reported significant changes in intracellular mitogen-activated protein kinase pathways from isolated NK cells. The purpose of this present investigation was to examine whether protein kinase genes have a role in abnormal NK cell intracellular signaling in CFS/ME.METHODMessenger RNA (mRNA) expression of 528 protein kinase genes in isolated NK cells was analyzed (nCounter GX Human Kinase Kit v2 (XT); NanoString Technologies) from moderate (n = 11; age, 54.9 ± 10.3 years) and severe (n = 12; age, 47.5 ± 8.0 years) CFS/ME patients (classified by the 2011 International Consensus Criteria) and nonfatigued controls (n = 11; age, 50.0 ± 12.3 years).RESULTSThe expression of 92 protein kinase genes was significantly different in the severe CFS/ME group compared with nonfatigued controls. Among these, 37 genes were significantly upregulated and 55 genes were significantly downregulated in severe CFS/ME patients compared with nonfatigued controls.CONCLUSIONSIn severe CFS/ME patients, dysfunction in protein kinase genes may contribute to impairments in NK cell intracellular signaling and effector function. Similar changes in protein kinase genes may be present in other cells, potentially contributing to the pathomechanism of this illness.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Chacko

Staines

Johnston

et al. 2016

Gene�Regul Syst Bio

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“…MTs are polar polymers comprising α/β-tubulin dimers that assemble end to end at centrosomes with the aid of the γ-tubulin complex (Oakley et al , 2015) to form tubules usually consisting of 13 protofilaments. The plus ends of MTs stochastically switch from growing to shrinking and back to growing via a process termed dynamic instability, and the minus ends are generally associated with the centrosome (Mitchison and Kirschner, 1984).…”

Section: Dynamic Microtubules In Neuronal Dendritesmentioning

confidence: 99%

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

Dent

2017

MBoC

117

104

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Microtubules (MTs) are cytoskeletal polymers composed of repeating subunits of tubulin that are ubiquitously expressed in eukaryotic cells. They undergo a stochastic process of polymerization and depolymerization from their plus ends termed dynamic instability. MT dynamics is an ongoing process in all cell types and has been the target for the development of several useful anticancer drugs, which compromise rapidly dividing cells. Recent studies also suggest that MT dynamics may be particularly important in neurons, which develop a highly polarized morphology, consisting of a single axon and multiple dendrites that persist throughout adulthood. MTs are especially dynamic in dendrites and have recently been shown to polymerize directly into dendritic spines, the postsynaptic compartment of excitatory neurons in the CNS. These transient polymerization events into dendritic spines have been demonstrated to play important roles in synaptic plasticity in cultured neurons. Recent studies also suggest that MT dynamics in the adult brain function in the essential process of learning and memory and may be compromised in degenerative diseases, such as Alzheimer’s disease. This raises the possibility of targeting MT dynamics in the design of new therapeutic agents.

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“…In living cells, de novo nucleation is suppressed so that nucleation of microtubules is favored to occur from nucleating structures that are usually components of “microtubule-organizing centers” such as the centrosome. The nucleating structures are called gamma-turcs (gamma tubulin ring complexes) because they consist of gamma tubulin, together with other proteins that combine with gamma-tubulin to form a template for the nucleation of new microtubules (2, 3). Gamma tubulin is a separate gene product from alpha or beta tubulin, and binds specifically to beta tubulin to establish the polarity orientation of the microtubule that elongates away from the nucleating structure.…”

Section: Microtubule Organization In Neuronsmentioning

confidence: 99%

Microtubules in health and degenerative disease of the nervous system

Matamoros

Baas

2016

Brain Research Bulletin

112

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Microtubules are essential for the development and maintenance of axons and dendrites throughout the life of the neuron, and are vulnerable to degradation and disorganization in a variety of neurodegenerative diseases. Microtubules, polymers of tubulin heterodimers, are intrinsically polar structures with a plus end favored for assembly and disassembly and a minus end less favored for these dynamics. In the axon, microtubules are nearly uniformly oriented with plus ends out, whereas in dendrites, microtubules have mixed orientations. Microtubules in developing neurons typically have a stable domain toward the minus end and a labile domain toward the plus end. This domain structure becomes more complex during neuronal maturation when especially stable patches of polyaminated tubulin become more prominent within the microtubule. Microtubules are the substrates for molecular motor proteins that transport cargoes toward the plus or minus end of the microtubule, with motor-driven forces also responsible for organizing microtubules into their distinctive polarity patterns in axons and dendrites. A vast array of microtubule-regulatory proteins impart direct and indirect changes upon the microtubule arrays of the neuron, and these include microtubule-severing proteins as well as proteins responsible for the stability properties of the microtubules. During neurodegenerative diseases, microtubule mass is commonly diminished, and the potential exists for corruption of the microtubule polarity patterns and microtubule-mediated transport. These ill effects may be a primary causative factor in the disease or may be secondary effects, but regardless, therapeutics capable of correcting these microtubule abnormalities have great potential to improve the status of the degenerating nervous system.

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γ-Tubulin complexes in microtubule nucleation and beyond

Cited by 115 publications

References 65 publications

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Of microtubules and memory: implications for microtubule dynamics in dendrites and spines

Microtubules in health and degenerative disease of the nervous system

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