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ELMO1

Official Full Name
engulfment and cell motility 1
Background
This gene encodes a member of the engulfment and cell motility protein family. These proteins interact with dedicator of cytokinesis proteins to promote phagocytosis and cell migration. Increased expression of this gene and dedicator of cytokinesis 1 may promote glioma cell invasion, and single nucleotide polymorphisms in this gene may be associated with diabetic nephropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Synonyms
ELMO1; engulfment and cell motility 1; CED12; CED-12; ELMO-1; engulfment and cell motility protein 1; ced-12 homolog 1; engulfment and cell motility 1 (ced 12 homolog, C. elegans); CED 12; ELMO 1; KIAA0281; MGC126406; CED12, CED-12, ELMO-1; engulfment and cell motility 1 (ced-12 homolog, C. elegans); zgc:85612; im:7151147; wu:fq24e08

Engulfment and cell motility 1(ELMO1), is a very conserved protein that mediates phagocytosis, migration and morphological changes in cells. ELMO1 is important for maintaining the homeostasis of organisms, and its abnormal expression is closely related to the clinical stage and prognosis of diabetic nephropathy, microbial infection, and malignant tumor. ELMO1 has been confirmed to be one of the sensitive genes of diabetic nephropathy and is also involved in the invasion and metastasis of tumor cells.

The Biological Role of ELMO1

The role of ELMO1 can be mainly reflected in the following aspects: (1) acting as a downstream substance of phosphatidylserine receptor cerebrovascular angiogenesis inhibitor 1 (BAI1) and synergizes with DOCK1 to activate the Rac1 downstream signaling pathway via Rac-GEF pathway, triggering cytoskeletal rearrangement and promoting integrin-mediated phagocytosis.; (2) promoting internalization of dead cells; (3) promoting neuronal growth factor-induced neurite outgrowth and participating in the morphogenesis of neuronal cells; (4) recruiting microtubule microfilament cross-linking factors on the surface of cell membranes to promote tubulin capture and ubiquitin-mediated formation of cellular pseudopods; (5) acting as a target for distant-less homeobox 1, Dlx1, and is selectively expressed in Reelin-positive [Re(+)] and Calretinin-positive [Cr(+)] interneurons, which are indispensable for the migration of activity-dependent intermediate neurons; (6) acting as a unique regulator of the endogenous mediator complex 31 (Med31), which is mainly located in the nucleus, increasing the expression of Med31 in the cytoplasm, promoting its ubiquitination, and jointly affecting the expression of cytokines IL10 and IL33.

Figure 1. ELMO1 directly transduces GPCR signaling to Rac1 to regulate F-actin dynamics in chemotaxing cells. (Youhong, et al. 2016)

ELMO1 and Diabetic Nephropathy

ELMO1 plays an important role in the pathogenesis of diabetic nephropathy (DN). Genome-wide association analysis (GWAS) and GoKinD study of Japanese (yellow), African American (black) and Caucasians (white) showed that mutations at the ELMO1 gene locus were associated with diabetic nephropathy. Genetic mutations in ELMO1 will result in increased expression of ELMO1 in the glomeruli of diabetic patients. The polymorphism site associated with DN of ELMO1 is at its transcription start position. The genetic polymorphism of ELMO1 is closely related to the development of glomerulosclerosis and the fibrosis process of the kidney under high glucose conditions. In addition, ELMO1 not only predicts the onset of kidney damage in diabetic nephropathy, but may also lead to kidney failure.

ELMO1 and Tumor Invasive Growth

ELMO1 is abnormally expressed in various malignant tumors including lung cancer, breast cancer, esophageal adenocarcinoma, ovarian cancer, thyroid cancer, rhabdomyosarcoma and glioma, and is closely related to the clinical stage and prognosis of the tumor. It is one of the genes associated with tumor cell migration.

Overexpression of ELMO1 was significantly positively correlated with the invasiveness of rhabdomyosarcoma. In ovarian cancer cell line SKOV3, downregulation of ELMO1 interacting protein DOCK180 directly leads to down-regulation of ELMO1, and cell proliferation, migration ability, and invasiveness are significantly inhibited, accompanied by changes in cell morphology, such as flaky pseudopodia and decreased formation of filopodia, suggesting that ELMO1 and DOCK180 support each other and synergistically stimulate the downstream effector Rac1, which regulates the malignant behavior of cell motility and ovarian cancer cells. Breast cancer studies have shown that expression of ELMO1 is associated with lymph node and distant metastasis, and knockout of ELMO1 can lead to lung metastasis in breast cancer.

References:

  1. Mauldin, J. P., Lu, M., Das, S., Park, D., Ernst, P. B., & Ravichandran, K. S. (2013). A link between the cytoplasmic engulfment protein elmo1 and the mediator complex subunit med31. Current Biology Cb, 23(2), 162-167.
  2. Youhong, W. , Xuehua, X. , Miao, P. , & Tian, J. . (2016). Elmo1 directly interacts with gβγ subunit to transduce gpcr signaling to rac1 activation in chemotaxis. Journal of Cancer, 7(8), 973-983.
  3. Sharma, K. R. , Heckler, K. , Stoll, S. J. , Hillebrands, J. L. , Kynast, K. , & Herpel, E. , et al. (2016). Elmo1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions. Scientific Reports, 6, 37172.

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