The Bipartite Rac1 Guanine Nucleotide Exchange Factor Engulfment and Cell Motility 1/Dedicator of Cytokinesis 180 (Elmo1/Dock180) Protects Endothelial Cells from Apoptosis in Blood Vessel Development

Schäker, Kathrin; Bartsch, Susanne; Patry, Christian; Stoll, Sandra J.; Hillebrands, Jan-Luuk; Wieland, Thomas; Krøll, Jens

doi:10.1074/jbc.m114.633701

Cited by 31 publications

(37 citation statements)

References 76 publications

(37 reference statements)

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“…3. Overexpression of ELMO11314 (Supplementary Figure 6) could beneficially restore the compromised pronephric structure within PDX1 morphants (Fig. 4A–D).…”

Section: Resultsmentioning

confidence: 96%

“…Recently, ELMO1 has been established to protect endothelial cells from apoptosis during angiogenesis14. It was hypothesized that a similar function is being performed by the protein in the renal system.…”

Section: Resultsmentioning

confidence: 99%

“…8). ELMO1 not only shields endothelial cells from apoptosis14, but also functions to protect glomerular cells from the phenomenon, under high glucose conditions. Hyperglycaemic conditions in zebrafish embryos caused by PDX1 knockdown16, do not induce ELMO1 expression within the pronephros.…”

Section: Discussionmentioning

confidence: 99%

“…Embryos were rehydrated and treated with Proteinase K (10 μg/ml, Roche) for 21 min. TUNEL protocol was hence followed as previously described14.…”

Section: Methodsmentioning

confidence: 99%

“…ELMO1 is expressed in the vasculature in zebrafish and loss-of-function experiments identified an important role for ELMO1 in early developmental vascular processes13. Recently, ELMO1 was shown to protect endothelial cells from apoptosis via activation of the Rac1/PAK/AKT signalling cascade in vitro and in vivo 14. ELMO1 has also been implicated in the development of ciliopathy-related phenotypes in zebrafish, by regulating Ezrin phosphorylation15.…”

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confidence: 99%

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ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions

Sharma

Heckler

Stoll

et al. 2016

Sci Rep

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Engulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients. In zebrafish, hyperglycaemia did not alter renal ELMO1 expression. However, hyperglycaemia leads to pathophysiological and functional alterations within the pronephros, which could be rescued via ELMO1 overexpression. Zebrafish ELMO1 crispants exhibited a renal pathophysiology due to increased apoptosis which could be rescued by the inhibition of apoptosis. In human samples, immunohistochemical staining of ELMO1 in nondiabetic, diabetic and polycystic kidneys localized ELMO1 in glomerular podocytes and in the tubules. However, ELMO1 was not specifically or distinctly regulated under either one of the disease conditions. Collectively, these results highlight ELMO1 as an important factor for glomerular protection and renal cell survival via decreasing apoptosis, especially under diabetic conditions.

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“…3. Overexpression of ELMO11314 (Supplementary Figure 6) could beneficially restore the compromised pronephric structure within PDX1 morphants (Fig. 4A–D).…”

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Embryos were rehydrated and treated with Proteinase K (10 μg/ml, Roche) for 21 min. TUNEL protocol was hence followed as previously described14.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions

Sharma

Heckler

Stoll

et al. 2016

Sci Rep

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High DOCK1 expression identifies a distinct prognostic subgroup of pediatric acute myeloid leukemia: Results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML‐05 trial

Yoshitomi,

Tsujimoto,

Ikeda

et al. 2024

Pediatric Blood & Cancer

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BackgroundThe molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in patients with AML that have helped to improve the risk stratification. However, developing new treatment strategies for relapsed/refractory acute myeloid leukemia (AML) is crucial due to its poor prognosis.ProcedureTo overcome this difficulty, we performed an assay for transposase‐accessible chromatin with sequencing (ATAC‐seq) in 10 AML patients with various gene alterations. ATAC‐seq is based on direct in vitro sequencing adaptor transposition into native chromatin, and is a rapid and sensitive method for integrative epigenomic analysis. ATAC‐seq analysis revealed increased accessibility of the DOCK1 gene in patients with AML harboring poor prognostic factors. Following the ATAC‐seq results, quantitative reverse transcription polymerase chain reaction was used to measure DOCK1 gene expression levels in 369 pediatric patients with de novo AML.ResultsHigh DOCK1 expression was detected in 132 (37%) patients. The overall survival (OS) and event‐free survival (EFS) among patients with high DOCK1 expression were significantly worse than those patients with low DOCK1 expression (3‐year EFS: 34% vs. 60%, p < .001 and 3‐year OS: 60% vs. 80%, p < .001). To investigate the significance of high DOCK1 gene expression, we transduced DOCK1 into MOLM14 cells, and revealed that cytarabine in combination with DOCK1 inhibitor reduced the viability of these leukemic cells.ConclusionsOur results indicate that a DOCK1 inhibitor might reinforce the effects of cytarabine and other anti‐cancer agents in patients with AML with high DOCK1 expression.

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Elmo1 function, linked to Rac1 activity, regulates peripheral neuronal numbers and myelination in zebrafish

Mikdache

Fontenas

Albadri

et al. 2019

Cell. Mol. Life Sci.

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The Bipartite Rac1 Guanine Nucleotide Exchange Factor Engulfment and Cell Motility 1/Dedicator of Cytokinesis 180 (Elmo1/Dock180) Protects Endothelial Cells from Apoptosis in Blood Vessel Development

Cited by 31 publications

References 76 publications

ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions

ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions

High DOCK1 expression identifies a distinct prognostic subgroup of pediatric acute myeloid leukemia: Results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML‐05 trial

Elmo1 function, linked to Rac1 activity, regulates peripheral neuronal numbers and myelination in zebrafish

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