Arginylation of ß-Actin Regulates Actin Cytoskeleton and Cell Motility

Karakozova, Marina; Kozak, Marina; Wong, Catherine C. L.; Bailey, Aaron O.; Yates, John R.; Mogilner, Alex; Zebroski, Henry; Kashina, Anna

doi:10.1126/science.1129344

Cited by 248 publications

(347 citation statements)

References 19 publications

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“…An example of such a protein is arginyltransferase, Ate1, whose knockout in mice results in embryonic lethality with specific defects in heart development and angiogenesis that suggest that this gene and the corresponding posttranslational modification plays a critical role in cell migration in situ (Kwon et al, 2002). In agreement with that, Ate1 has been recently shown to regulate actin cytoskeleton, lamella formation, and lamellipodial protrusion (Karakozova et al, 2006), however the exact role of Ate1 in embryogenesis and cell motility remains to be uncovered.…”

Section: Migration-dependent Developmental Defects Key Cell Migrationmentioning

confidence: 86%

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Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

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117

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Cell migration is an evolutionarily conserved mechanism that underlies the development and functioning of uni-and multicellular organisms and takes place in normal and pathogenic processes, including various events of embryogenesis, wound healing, immune response, cancer metastases, and angiogenesis. Despite the differences in the cell types that take part in different migratory events, it is believed that all of these migrations occur by similar molecular mechanisms, whose major components have been functionally conserved in evolution and whose perturbation leads to severe developmental defects. These mechanisms involve intricate cytoskeleton-based molecular machines that can sense the environment, respond to signals, and modulate the entire cell behavior. A big question that has concerned the researchers for decades relates to the coordination of cell migration in situ and its relation to the intracellular aspects of the cell migratory mechanisms. Traditionally, this question has been addressed by researchers that considered the intra-and extracellular mechanisms driving migration in separate sets of studies. As more data accumulate researchers are now able to integrate all of the available information and consider the intracellular mechanisms of cell migration in the context of the developing organisms that contain additional levels of complexity provided by extracellular regulation. This review provides a broad summary of the existing and emerging data in the cell and developmental biology fields regarding cell migration during development.

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Section: Migration-dependent Developmental Defects Key Cell Migrationmentioning

confidence: 86%

“…An emerging role in cell motility belongs to post-translational arginylation of actin and actin-associated proteins (Wong et al, 2007). Arginylation has been shown to modulate lamella formation in motile cells and determine directionality and speed of cell migration (Karakozova et al, 2006).…”

Section: Posttranslational Regulation Of Cell Migrationmentioning

confidence: 99%

Cell biology of embryonic migration

Kurosaka¹,

Kashina²

2008

Birth Defects Research Pt C

Self Cite

117

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“…19 They also have different post-translational modifications, for instance arginylation of b-actin, but not of g-actin. 20 ACTB and ACTG1 can copolymerize easily in vitro 14 and are likely to act similarly in vivo, at least in lamellipodia. 21 Consequently, ACTB and ACTG1 have both cooperative interactions and partially non-redundant functions.…”

Section: Baraitser-winter Cerebrofrontofacial Syndromementioning

confidence: 99%

Baraitser–Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases

Verloes¹,

Donato²,

et al. 2014

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Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode b-and c-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancerpredisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.

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“…49 These new roles of tRNAs have been observed in prokaryotes as well as eukaryotes, and they are involved in various cellular phenomena, including haeme and chlorophyll biosynthesis, antibiotic cellular permeability, energy metabolism, amino acid biosynthesis and protein degradation, reverse transcription of viruses, cell apoptosis and survival, and cancer progression. 4-6 , 10 , 37 , 50-55 In this study, we investigated the novel functions of tRNAs, especially tRNA Leu , which promoted cell proliferation via RSK/MSK signaling.…”

Section: Discussionmentioning

confidence: 99%

Transfer-RNA-mediated enhancement of ribosomal proteins S6 kinases signaling for cell proliferation

et al. 2018

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While transfer-RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNALeu overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNALeu and was independent to mTOR (mammalian target of rapamycin) signaling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNALeu overexpression. Through SILAC (stable isotope labeling by/with amino acids in cell culture) and combined mass spectrometry analysis, we identified EBP1 (ErbB3-binding protein 1) as the tRNALeu-binding protein. We suspected that the overexpression of free tRNALeu would reinforce ErbB2/ErbB3 signaling pathway by disturbing the interaction between ErbB3 and EBP1, resulting in RSK1/MSK2 phosphorylation, improving cell proliferation and resistance to death. Analysis of samples from patients with breast cancer also indicated an association between tRNALeu overexpression and the ErbB2-positive population. Our results suggested a possible link between tRNALeu overexpression and RSK1/MSK2 activation and ErbB2/ErbB3 signaling.

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Arginylation of ß-Actin Regulates Actin Cytoskeleton and Cell Motility

Cited by 248 publications

References 19 publications

Cell biology of embryonic migration

Cell biology of embryonic migration

Baraitser–Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases

Transfer-RNA-mediated enhancement of ribosomal proteins S6 kinases signaling for cell proliferation

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