EMC1 Protein in Retinal Vascular Development

Endoplasmic reticulum (ER) membrane protein complex (EMC) was discovered in yeast as a cluster of six components that play critical functions in ER homeostasis. The human EMC complex is a highly conserved cluster of ten EMC subunits (EMC1-EMC10), and depleting any one of EMC1, EMC2, EMC3, EMC5, or EMC6 entirely disturbed the EMC complex. Recent research has shown that EMC not only functions as an insertase for C-terminal transmembrane domains (TMDs) of tail-anchored (TA) membrane proteins, but also mediates the expression of non-TA membrane proteins such as G protein-coupled receptors (GPCRs), which are required for vessel myogenic tone and vascular permeability.

The co-translational insertion of freshly generated multi-transmembrane proteins requires the Endoplasmic reticulum (ER) membrane protein complex (EMC). Multiple illnesses have been linked to impaired EMC1 function in various cell types.

Researchers from the University of Electronic Science and Technology of China discovered a significant association between the EMC1 protein and retinal vascular development. Mutations in the EMC1 gene appear to be linked to FEVR, a serious eye disorder. The revelation opens up new therapeutic possibilities for treating this condition and other vascular abnormalities.

Depletion of Emc1 in endothelial cells in mice produces major abnormalities in retinal artery formation, including diminished vascular expansion and retinal hemorrhage, according to researchers. This defect is closely related to the Wnt signaling system, a key regulator of blood vessel development whose gene activity is changed when EMC1 is disrupted. This observation motivated researchers to look into the EMC1 gene in FEVR patients, which led to the discovery of a genetic mutation in two related individuals, indicating a possible genetic link. Notably, treating EMC1-depleted cells with LiCl, a Wnt signaling pathway activator, alleviated some of the negative effects, implying possible treatment routes for illnesses linked with EMC1 malfunction. The EMC1 protein has emerged as a critical element in retinal blood circulation.

This study enhances our understanding of the beginning of FEVR and broadens the scope of targeted therapeutic therapies. Researchers expect that by focusing on the Wnt signaling pathway, they will be able to design treatments that can reduce or even repair the vascular abnormalities associated with impaired EMC1 function.

Exciting Discovery in Retinal Vascular Development

For more information: Defective EMC1 drives abnormal retinal angiogenesis via Wnt/β-catenin signaling and may be associated with the pathogenesis of familial exudative vitreoretinopathy. Genes & Diseases.

doi.org/10.1016/j.gendis.2022.10.003.