Microtubule Severing by Elongation Factor 1α

Shiina, Nobuyuki; Gotoh, Yukiko; Kubomura, Nobuko; Iwamatsu, Akihiro; Nishida, Eisuke

doi:10.1126/science.7939665

Cited by 238 publications

(177 citation statements)

References 27 publications

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“…In the EF1␣-overproducing cells, microtubules curled around the ends of the cell. The effect of EF1␣ overproduction on the microtubule cytoskeleton seems to be inconsistent with the previous observation that EF1␣ possesses microtubule-severing activity (Shiina et al 1994). Curled microtubules were frequently observed in the fission yeast alp (Radcliffe et al 1998;Hirata & Toda, unpublished observations) or tea1 mutant cells (Mata & Nurse 1997).…”

Section: Discussioncontrasting

confidence: 52%

“…EF1␣ has been isolated as an actin-binding and -bundling protein from Dictyostelium Yang et al 1990), a cellular slime mold; Physarum (Itano & Hatano 1991), a ciliate; Tetrahymena (Kurasawa et al 1996); and sea urchin eggs (Fujimoto & Mabuchi 1998). EF1␣ has also been shown to become localized in the mitotic apparatus of the sea urchin egg (Kuriyama et al 1990;Ohta et al 1990), and to possess microtubule-severing activity (Shiina et al 1994) and the activity to make fibroblasts highly susceptible to transformation (Tatsuka et al 1992). Recently, it was shown that Saccharomyces cerevisiae EF1␣ directly interacts with Bni1, which is the target of the small GTP-binding protein Rho1, and has been implicated in the polymerization of actin (Umikawa et al 1998).…”

Section: Introductionmentioning

confidence: 99%

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Overproduction of elongation factor 1α, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast

et al. 1999

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Background: Elongation factor 1␣ (EF1␣), an essential component of the eukaryotic translational machinery, has been shown to possess various biochemical and biological activities, including F-actin-binding and -bundling, microtubulesevering, and the activity of making fibroblasts highly susceptible to transformation. However, our understanding of the biological significance of EF1␣ with respect to these various biochemical or biological activities remains limited. Here we report the identification of EF1␣-encoding genes as genes whose over-expression causes aberrant cell morphology in fission yeast.

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Section: Discussioncontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Overproduction of elongation factor 1α, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast

et al. 1999

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“…EF-1a is a GTPase that has multiple and divergent roles in cell physiology affecting the cytoskeleton, peptide synthesis and protein degradation. 18,22,23 We have found that the enforced expression of EF-1a can promote long-term viability from growth factor withdrawal-induced death in proportion to its level of expression. EF-1a protection does not extend to nuclear DNA damaging agents nor activation of TNF death receptors.…”

Section: Discussionmentioning

confidence: 99%

Elongation factor-1 alpha is a selective regulator of growth factor withdrawal and ER stress-induced apoptosis

2002

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To identify genes that contribute to apoptotic resistance, IL-3 dependent hematopoietic cells were transfected with a cDNA expression library and subjected to growth factor withdrawal. Transfected cells were enriched for survivors over two successive rounds of IL-3 withdrawal and reconstitution, resulting in the identification of a full-length elongation factor 1 alpha (EF-1a) cDNA. Ectopic EF-1a expression conferred protection from growth factor withdrawal and agents that induce endoplasmic reticulum stress, but not from nuclear damage or death receptor signaling. Overexpression of EF-1a did not lead to growth factor independent cell proliferation or global alterations in protein levels or rates of synthesis. These findings suggest that overexpression of EF-1a results in selective resistance to apoptosis induced by growth factor withdrawal and ER stress.

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“…This may provide a mechanism by which muscarinic activation can increase dendritic translation and may also allow for muscarinic regulation of other functions of eEF1A2. eEF1A has been demonstrated to bind and bundle actin (49), bind microtubules (50,51), bind calmodulin (52), and regulate apoptosis (53). Also, this interaction may provide a molecular mechanism underlying functional differences between the two closely related mAChR subtypes, M 2 and M 4 .…”

Section: Discussionmentioning

confidence: 99%

Novel Interaction between the M4 Muscarinic Acetylcholine Receptor and Elongation Factor 1A2

McClatchy¹,

Knudsen²,

Clark³

et al. 2002

Journal of Biological Chemistry

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The activation of the muscarinic acetylcholine receptor (mAChR) family, consisting of five subtypes (M 1 -M 5 ), produces a variety of physiological effects throughout the central nervous system. However, the role of each individual subtype remains poorly understood. To further elucidate signal transduction pathways for specific subtypes, we used the most divergent portion of the subtypes, the intracellular third (i3) loop, as bait to identify interacting proteins. Using a brain pull-down assay, we identify elongation factor 1A2 (eEF1A2) as a specific binding partner to the i3 loop of M 4 , and not to M 1 or M 2 .In addition, we demonstrate a direct interaction between these proteins. In the rat striatum, the M 4 mAChR colocalizes with eEF1A2 in the soma and neuropil. In PC12 cells, endogenous eEF1A2 co-immunoprecipitates with the endogenous M 4 mAChR, but not with the endogenous M 1 mAChR. In our in vitro model, M 4 dramatically accelerates nucleotide exchange of eEF1A2, a GTP-binding protein. This indicates the M 4 mAChR is a guanine exchange factor for eEF1A2. eEF1A2 is an essential GTP-binding protein for protein synthesis. Thus, our data suggest a novel role for M 4 in the regulation of protein synthesis through its interaction with eEF1A2.In the central nervous system, the muscarinic acetylcholine receptors (mAChR) 1 play crucial roles in learning, memory, movement, analgesia, and sleep (1-3). Dysfunction in mAChR signaling has been implicated in brain disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia (4 -6). The mAChRs belong to the G-protein-coupled receptor (GPCR) superfamily. Upon agonist binding, GPCRs bind and activate heterotrimeric G-proteins, which in turn activate various downstream targets. There are two distinct, well characterized G-protein signaling pathways activated by the five mAChR subtypes. M 1 , M 3 , and M 5 couple to G q , which stimulates phospholipase C-␤, and thus releases calcium from intracellular stores and activates protein kinase C (7, 8). M 2 and M 4 are coupled to G i/o , which regulates adenylate cyclase (9). These subtypes are expressed throughout the brain, and, in some brain regions, multiple subtypes are expressed in individual neurons (10). The diversity of physiological effects and the overlapping expression pattern of the muscarinic receptor subtypes suggest that there are signaling pathways initiated by the mAChRs independent of these two heterotrimeric G-protein pathways.Signaling pathways independent of heterotrimeric G-proteins have been reported throughout the GPCR superfamily (11-14). Evidence supporting this hypothesis stems from the identification of novel binding partners of GPCRs other than the traditional heterotrimeric G-proteins. Within the muscarinic family in particular, there is an especially large body of evidence to suggest the existence of nontraditional signaling pathways. There are many reports of G-protein-independent regulation of ion channels by mAChRs (15-18). Moreover, the M 3 mAChR has been found to associate ...

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Microtubule Severing by Elongation Factor 1α

Cited by 238 publications

References 27 publications

Overproduction of elongation factor 1α, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast

Overproduction of elongation factor 1α, an essential translational component, causes aberrant cell morphology by affecting the control of growth polarity in fission yeast

Elongation factor-1 alpha is a selective regulator of growth factor withdrawal and ER stress-induced apoptosis

Novel Interaction between the M4 Muscarinic Acetylcholine Receptor and Elongation Factor 1A2

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