Nebulin and N-WASP Cooperate to Cause IGF-1–Induced Sarcomeric Actin Filament Formation

Science ◽  
2010 ◽  
Vol 330 (6010) ◽  
pp. 1536-1540 ◽  
Author(s):  
Kazunori Takano ◽  
Haruko Watanabe-Takano ◽  
Shiro Suetsugu ◽  
Souichi Kurita ◽  
Kazuya Tsujita ◽  
...  
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Muscle Hypertrophy ◽  
Glycogen Synthase ◽  
Akt Signaling ◽  
Glycogen Synthase Kinase 3Β ◽  
Filament Formation ◽  
Phosphatidylinositol 3 Kinase ◽  
Actin Nucleation ◽  
Signaling Mechanisms

Insulin-like growth factor 1 (IGF-1) induces skeletal muscle maturation and enlargement (hypertrophy). These responses require protein synthesis and myofibril formation (myofibrillogenesis). However, the signaling mechanisms of myofibrillogenesis remain obscure. We found that IGF-1–induced phosphatidylinositol 3-kinase–Akt signaling formed a complex of nebulin and N-WASP at the Z bands of myofibrils by interfering with glycogen synthase kinase-3β in mice. Although N-WASP is known to be an activator of the Arp2/3 complex to form branched actin filaments, the nebulin–N-WASP complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-WASP was required for IGF-1–induced muscle hypertrophy. These findings present the mechanisms of IGF-1–induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation.

scholarly journals Stimulus-response uncoupling in the neutrophil. Adenosine A2-receptor occupancy inhibits the sustained, but not the early, events of stimulus transduction in human neutrophils by a mechanism independent of actin-filament formation

1992 ◽  
Vol 281 (3) ◽  
pp. 631-635 ◽  
Author(s):  
B N Cronstein ◽  
K A Haines
Keyword(s):  
Actin Filament ◽  
Adenosine Receptor ◽  
Actin Filaments ◽  
Cytochalasin B ◽  
Receptor Occupancy ◽  
Neutrophil Activation ◽  
Filament Formation ◽  
Stimulus Response ◽  
Adenosine A2 Receptor ◽  
A2 Receptors

Generation of superoxide anion (O2-) in response to occupancy of neutrophil chemoattractant receptors requires both early events (‘triggering’) and sustained signals (‘activation’). We have previously demonstrated that occupancy of adenosine A2 receptors inhibits O2- generation by neutrophils. In parallel, adenosine-receptor occupancy promotes association of bound N-formylmethionyl-leucyl-phenylalanine (fMLP) receptors with the cytoskeleton, a process associated with termination of neutrophil activation (stimulus-response uncoupling). We undertook this study to determine whether inhibition of neutrophil function by adenosine-receptor occupancy requires intact actin filaments and to examine the effect of adenosine-receptor occupancy on the stimulated generation of intracellular signals involved in neutrophil triggering and activation. Occupancy of adenosine A2 receptors by 5′-N-ethylcarboxamidoadenosine (NECA, 1 microM) significantly increased (130 +/- 1% of control, P less than 0.001, n = 3) association of [3H]fMLP with cytoskeletal preparations. Cytochalasin B (5 micrograms/ml), an agent which disrupts actin filaments, completely blocked association of [3H]fMLP with cytoskeletal preparations, as previously reported. However, NECA markedly increased association of [3H]fMLP with the cytoskeleton even in the presence of cytochalasin B (P less than 0.0002). Moreover, NECA did not significantly affect either the early (30s) or the late (5 min) formation of actin filaments after stimulation by chemoattractant (fMLP, 0.1-100 nM). Cytochalasin B markedly inhibited actin-filament formation by stimulated neutrophils, and NECA did not reverse the effect of cytochalasin B on actin-filament formation. Adenosine-receptor occupancy did not affect the rapid peak in diacylglycerol generation (less than or equal to 15 s) from either [3H]arachidonate- or [14C]glycerol-labelled phospholipid pools. However, as would be predicted if occupancy of the adenosine receptor was a signal for early termination of cell activation, NECA (1 microM) markedly diminished the slow sustained generation of diacylglycerol. These results suggest that adenosine-A2-receptor occupancy does not affect triggering of the neutrophil, but that occupancy of adenosine receptors is an early signal for the termination of neutrophil activation, i.e. the ‘premature’ finish of signal transduction. Moreover, these data indicate that at least two pathways are available for increasing the association of ligated chemoattractant receptors with the cytoskeleton of neutrophils: F-actin-dependent and -independent.

scholarly journals Myeloid Cell IL-10 Production in Response to Leishmania Involves Inactivation of Glycogen Synthase Kinase-3β Downstream of Phosphatidylinositol-3 Kinase

2011 ◽  
Vol 188 (1) ◽  
pp. 367-378 ◽  
Author(s):  
Devki Nandan ◽  
Carolina Camargo de Oliveira ◽  
Alireza Moeenrezakhanlou ◽  
Martin Lopez ◽  
Judith M. Silverman ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Myeloid Cell ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration

2004 ◽  
Vol 286 (1) ◽  
pp. C153-C163 ◽  
Author(s):  
Yong Qian ◽  
Linda Corum ◽  
Qiao Meng ◽  
John Blenis ◽  
Jenny Z. Zheng ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Filament ◽  
Actin Filaments ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Chicken Embryo Fibroblast ◽  
Active Form ◽  
Specific Inhibitor ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Activity

This study was designed to identify the molecular mechanisms of phosphatidylinositol 3-kinase (PI3K)-induced actin filament remodeling and cell migration. Expression of active forms of PI3K, v-P3k or Myr-P3k, was sufficient to induce actin filament remodeling to lead to an increase in cell migration, as well as the activation of Akt in chicken embryo fibroblast (CEF) cells. Either the inhibition of PI3K activity using a PI3K-specific inhibitor, LY-294002, or the disruption of Akt activity restored the integrity of actin filaments in CEF cells and inhibited PI3K-induced cell migration. We also found that expression of an activated form of Akt (Myr-Akt) was sufficient to remodel actin filaments to lead to an increase in cell migration, which was unable to be inhibited by the presence of LY-294002. Furthermore, we found that p70S6K1 kinase was a downstream molecule that can mediate the effects of both PI3K and Akt on actin filaments and cell migration. Overexpression of an active form of p70S6K1 was sufficient to induce actin filament remodeling and cell migration in CEF cells, which requires Rac activity. These results demonstrate that activation of PI3K activity alone is sufficient to remodel actin filaments to increase cell migration through the activation of Akt and p70S6K1 in CEF cells.

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