Csrp1 regulates dynamic cell movements of the mesendoderm and cardiac mesoderm through interactions with Dishevelled and Diversin

Miyasaka, Kota; Kida, Yasuyuki S.; Sato, Takayuki; Minami, Mari; Ogura, Toshihiko

doi:10.1073/pnas.0702000104

Cited by 48 publications

(42 citation statements)

References 49 publications

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“…Of the most relevant findings, metabolic pathway analysis suggests that ketone-body formation is upregulated through an alternative pathway. Starvation and diabetes mellitus induce an upregulation of glucocorticoid signaling, resulting in elevated levels of Pdk4, 42 which we also observed in our study. Pdk4 is the key mediator in preventing the conversion of pyruvate to acetyl-CoA by inhibiting pyruvate dehydrogenase complex C. In the liver, this inhibition enables ketone-body synthesis from fatty acids and ketogenic amino acids rather than 3 carbon compounds, which are then available for gluconeogenesis in the liver to maintain blood glucose levels.…”

Section: Discussionsupporting

confidence: 75%

Proteome-Based Systems Biology Analysis of the Diabetic Mouse Aorta Reveals Major Changes in Fatty Acid Biosynthesis as Potential Hallmark in Diabetes Mellitus–Associated Vascular Disease

Husi

Agtmael

Mullen

et al. 2014

Circ Cardiovasc Genet

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The molecular mechanisms, as they are currently known, of the development of these vascular lesions during hyperglycemia are complex, involving an increase in Background-Macrovascular complications of diabetes mellitus are a major risk factor for cardiovascular morbidity and mortality. Currently, studies only partially described the molecular pathophysiology of diabetes mellitus-associated effects on vasculature. However, better understanding of systemic effects is essential in unraveling key molecular events in the vascular tissue responsible for disease onset and progression. Methods and Results-Our overall aim was to get an all-encompassing view of diabetes mellitus-induced key molecular changes in the vasculature. An integrative proteomic and bioinformatics analysis of data from aortic vessels in the lowdose streptozotocin-induced diabetic mouse model (10 animals) was performed. We observed pronounced dysregulation of molecules involved in myogenesis, vascularization, hypertension, hypertrophy (associated with thickening of the aortic wall), and a substantial reduction of fatty acid storage. A novel finding is the pronounced downregulation of glycogen synthase kinase-3β (Gsk3β) and upregulation of molecules linked to the tricarboxylic acid cycle (eg, aspartate aminotransferase [Got2] and hydroxyacid-oxoacid transhydrogenase [Adhfe1]). In addition, pathways involving primary alcohols and amino acid breakdown are altered, potentially leading to ketone-body production. A number of these findings were validated immunohistochemically. Collectively, the data support the hypothesis that in this diabetic model, there is an overproduction of ketone-bodies within the vessels using an alternative tricarboxylic acid cycle-associated pathway, ultimately leading to the development of atherosclerosis. Conclusions-Streptozotocin-induced diabetes mellitus in animals leads to a reduction of fatty acid biosynthesis and an upregulation of an alternative ketone-body formation pathway. This working hypothesis could form the basis for the development of novel therapeutic intervention and disease management approaches. proinflammatory signals (eg, activation of nuclear factor-κB, adhesion molecules, tumor necrosis factor-α, interleukin-1β and interleukin-6). 6 Downstream of these proinflammatory factors extracellular signal-regulated protein kinase-1, c-Jun NH2-terminal protein kinase-1 and -2, and p38 are activated. 7A further hallmark in the development of diabetic vascular lesions is the production of reactive oxygen species, resulting in inactivation of nitric oxide and appearance of advanced glycation end-products, further aggravating vascular tissue damage. 8 Several proteins have been proposed as targets for hyperglycemic changes in the vascular smooth muscle cells, including protein kinase C and the inositol trisphosphate-and ryanodine receptors.9 Inositol 1,4,5-trisphosphate-sensitive and ryanodine-sensitive stores are the major contributors to Ca 2+ homeostasis in vascular smooth muscle cell. 10 The complexity of the v...

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Section: Discussionsupporting

confidence: 75%

Proteome-Based Systems Biology Analysis of the Diabetic Mouse Aorta Reveals Major Changes in Fatty Acid Biosynthesis as Potential Hallmark in Diabetes Mellitus–Associated Vascular Disease

Husi

Agtmael

Mullen

et al. 2014

Circ Cardiovasc Genet

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“…Although a primary role of non-canonical Wnt signaling was to govern convergence and extension movements, studies had also shown that the three Wnt noncanonical ligands, wnt4a, wnt11, and wnt11r, redundantly regulated midline convergence of organ primordia, in zebrafish embryos (31,41). In this study, we showed that the midline migration of heart precursors and pancreas precursors required expression of eaf1 and eaf2/u19 (Fig.…”

Section: Discussionmentioning

confidence: 62%

Zebrafish eaf1 and eaf2/u19 Mediate Effective Convergence and Extension Movements through the Maintenance of wnt11 and wnt5 Expression

Liu¹,

Hu²,

Wang

et al. 2009

Journal of Biological Chemistry

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Studies have attributed several functions to the Eaf family, including tumor suppression and eye development. Given the potential association between cancer and development, we set forth to explore Eaf1 and Eaf2/U19 activity in vertebrate embryogenesis, using zebrafish. In situ hybridization revealed similar eaf1 and eaf2/u19 expression patterns. Morpholino-mediated knockdown of either eaf1 or eaf2/u19 expression produced similar morphological changes that could be reversed by ectopic expression of target or reciprocal-target mRNA. However, combination of Eaf1 and Eaf2/U19 (Eafs)-morpholinos increased the severity of defects, suggesting that Eaf1 and Eaf2/U19 only share some functional redundancy. The Eafs knockdown phenotype resembled that of embryos with defects in convergence and extension movements. Indeed, knockdown caused expression pattern changes for convergence and extension movement markers, whereas cell tracing experiments using kaeda mRNA showed a correlation between Eafs knockdown and cell migration defects. Cardiac and pancreatic differentiation markers revealed that Eafs knockdown also disrupted midline convergence of heart and pancreatic organ precursors. Noncanonical Wnt signaling plays a key role in both convergence and extension movements and midline convergence of organ precursors. We found that Eaf1 and Eaf2/U19 maintained expression levels of wnt11 and wnt5. Moreover, wnt11 or wnt5 mRNA partially rescued the convergence and extension movement defects occurring in eafs morphants. Wnt11 and Wnt5 converge on rhoA, so not surprisingly, rhoA mRNA more effectively rescued defects than either wnt11 or wnt5 mRNA alone. However, the ectopic expression of wnt11 and wnt5 did not affect eaf1 and eaf2/u19 expression. These data indicate that eaf1 and eaf2/u19 act upstream of noncanonical Wnt signaling to mediate convergence and extension movements. EAF1 (ELL-associated factor 1) was first discovered through its ability to associate with the protein ELL (eleven-nineteen lysine-rich leukemia), a fusion partner of MLL in the t(11; 19)(q23;p13.1) chromosomal translocation associated with acute myeloid leukemia (1, 2). Subsequent studies found a second binding partner for ELL, EAF2, which was independently identified as an androgen up-regulated gene in the rat prostate and named human up-regulated 19 (U19) (3, 4). ELL binds to RNA polymerase II and acts as a transcriptional elongation factor whose targeted deletion leads to embryonic lethality in mice (5, 6). Both EAF1 and EAF2, which share significant sequence homology, stimulate ELL elongation activity (7). Studies by Luo et al. (8) argued that EAF proteins are important in MLL-ELL leukemogenesis, whereas our previous studies showed that EAF2/U19 inhibits xenograft prostate tumor growth and undergoes down-regulation in prostate cancer cell lines (9). These findings link the EAF2/U19 gene with two major human cancers: prostate cancer and acute myeloid leukemia. To investigate the function EAF2/U19 in vivo, we constructed a murine knock-out model. The EAF2...

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“…CRP1 has been reported in many different cellular functions: acting as a transcriptional cofactor (Chang et al, 2003), suppressing cell proliferation, protecting cells from stress-induced death (Latonen et al, 2008), regulating cell movement during zebrafish development (Miyasaka et al, 2007), and promoting neointima formation (Lilly et al, 2010). It has also been demonstrated that CRP1 regulates actin filament bundling via direct interaction with actin (Tran et al, 2005;Jang and Greenwood, 2009).…”

Section: Introductionmentioning

confidence: 99%

CRP1, a Protein Localized in Filopodia of Growth Cones, Is Involved in Dendritic Growth

Ma¹,

Greenwood²,

Schachner³

2011

J. Neurosci.

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The cysteine-rich protein (CRP) family is a subgroup of LIM domain proteins. CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells. Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons. Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons. Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity. Expression of CRP1 with a constitutively active form of Cdc42, a GTPase involved in filopodia formation, increases filopodia formation in COS-7 cells, suggesting cooperation between the two proteins. Moreover, we demonstrate that neuronal activity upregulates CRP1 expression in hippocampal neurons via Ca 2ϩ influx after depolarization. Ca 2ϩ /calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein mediate the Ca 2ϩ -induced upregulation of CRP1 expression. Furthermore, CRP1 is required for the dendritic growth induced by Ca 2ϩ influx or CaMKIV. Together, these data are the first to demonstrate a role for CRP1 in dendritic growth.

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Csrp1 regulates dynamic cell movements of the mesendoderm and cardiac mesoderm through interactions with Dishevelled and Diversin

Cited by 48 publications

References 49 publications

Proteome-Based Systems Biology Analysis of the Diabetic Mouse Aorta Reveals Major Changes in Fatty Acid Biosynthesis as Potential Hallmark in Diabetes Mellitus–Associated Vascular Disease

Proteome-Based Systems Biology Analysis of the Diabetic Mouse Aorta Reveals Major Changes in Fatty Acid Biosynthesis as Potential Hallmark in Diabetes Mellitus–Associated Vascular Disease

Zebrafish eaf1 and eaf2/u19 Mediate Effective Convergence and Extension Movements through the Maintenance of wnt11 and wnt5 Expression

CRP1, a Protein Localized in Filopodia of Growth Cones, Is Involved in Dendritic Growth

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