ELMOD2 is a GTPase-activating protein (GAP) with uniquely broad specificity for ARF family GTPases. It is involved in multiple cellular pathways, such as mitochondrial fusion, microtubule stability, cytokinesis, cilia-related processes, and lipid metabolism. Its role in these processes is crucial for maintaining normal cellular functions [1,2,3,4]. Genetic models, especially knockout mouse models, have been instrumental in studying its functions.

In mouse embryonic fibroblasts with ELMOD2 deletion, there were increased ciliation, multiciliation, abnormal ciliary morphology and signaling, as well as loss of centrosome cohesion. These defects could be reversed by increasing ARL2 activity or overexpressing Rootletin, indicating that ELMOD2, ARL2, and Rootletin act in a common pathway regulating ciliary licensing [1]. Loss of ELMOD2 in mouse oocytes led to severe meiotic delay, abnormal chromosomal segregation, decreased oocyte maturation and fertilization rates, likely by regulating mitochondrial dynamics [5]. In adipocytes, knockdown of ELMOD2 increased ATGL in lipid droplets and decreased cellular triglycerides, suggesting its role in lipid metabolism [3].

In conclusion, ELMOD2 plays essential roles in multiple biological processes, including ciliogenesis, meiotic progression in oocytes, and lipid metabolism. The use of gene-knockout mouse models has been vital in uncovering these functions. These findings may have implications for understanding diseases related to ciliary defects, female infertility, and lipid-metabolism disorders [1,3,5].

References:

1. Turn, Rachel E, Linnert, Joshua, Gigante, Eduardo D, Caspary, Tamara, Kahn, Richard A. 2021. Roles for ELMOD2 and Rootletin in ciliogenesis. In Molecular biology of the cell, 32, 800-822. doi:10.1091/mbc.E20-10-0635. https://pubmed.ncbi.nlm.nih.gov/33596093/

2. Schiavon, Cara R, Turn, Rachel E, Newman, Laura E, Kahn, Richard A. 2019. ELMOD2 regulates mitochondrial fusion in a mitofusin-dependent manner, downstream of ARL2. In Molecular biology of the cell, 30, 1198-1213. doi:10.1091/mbc.E18-12-0804. https://pubmed.ncbi.nlm.nih.gov/30865555/

3. Suzuki, Michitaka, Murakami, Tatsuro, Cheng, Jinglei, Fukata, Masaki, Fujimoto, Toyoshi. 2015. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment. In Molecular biology of the cell, 26, 2333-42. doi:10.1091/mbc.E14-11-1504. https://pubmed.ncbi.nlm.nih.gov/25904333/

4. Turn, Rachel E, East, Michael P, Prekeris, Rytis, Kahn, Richard A. 2020. The ARF GAP ELMOD2 acts with different GTPases to regulate centrosomal microtubule nucleation and cytokinesis. In Molecular biology of the cell, 31, 2070-2091. doi:10.1091/mbc.E20-01-0012. https://pubmed.ncbi.nlm.nih.gov/32614697/

5. Zhou, Chun-Xiang, Shi, Li-Ya, Li, Rui-Chao, Ying, Xiao-Yan, Zhang, Dong. 2017. GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes. In Cell cycle (Georgetown, Tex.), 16, 852-860. doi:10.1080/15384101.2017.1304329. https://pubmed.ncbi.nlm.nih.gov/28324667/