Abstract
Guanine nucleotide exchange factors (GEFs) activate GTPases by stimulating the release of guanosine diphosphate to permit the binding of guanosine triphosphate. ARHGEF3 or XPLN (exchange factor found in platelets, leukemic, and neuronal tissues) is a selective guanine nucleotide exchange factor for Rho GTPases (RhoGEFs) that activates RhoA and RhoB but not RhoC, RhoG, Rac1, or Cdc42. ARHGEF3 contains the diffuse B-cell lymphoma homology and pleckstrin homology domains but lacks similarity with other known functional domains. ARHGEF3 also binds the mammalian target of rapamycin complex 2 (mTORC2) and subsequently inhibits mTORC2 and Akt. In vivo investigation has also indicated the communication between ARHGEF3 and autophagy-related muscle pathologies. Moreover, studies on genetic variation in ARHGEF3 and genome-wide association studies have predicted exciting novel roles of ARHGEF3 in controlling bone mineral density, platelet formation and differentiation, and Hirschsprung disease. In conclusion, we hypothesized that additional biochemical and functional studies are required to elucidate the detailed mechanism of ARHGEF3-related pathologies and therapeutics.
Highlights
ARHGEF3 was identified as RhoGEF (Rho guanine nucleotide exchange factor) for Rho GTPases through an expressed sequence tag) database search, using the diffuse B-cell lymphoma (Dbl) homology (DH) domain query in the BLASTN system (Thiesen et al, 2000)
The present review provides a complete understanding of the intricacies of genetic association networks engaged in ARHGEF3-related pathologies, prompting advancements in potential treatment modalities via mechanistic investigations
The DH-pleckstrin homology (PH) domains of ARHGEF3 share over 69% sequence similarity with those of neuroepithelial cell transforming gene 1 (Net1), which belongs to the diffuse B-cell lymphoma (Dbl) family (Murayama et al, 2012)
Summary
ARHGEF3 (or XPLN, exchange factor found in platelets, leukemic, and neuronal tissues) was identified as RhoGEF (Rho guanine nucleotide exchange factor) for Rho GTPases through an expressed sequence tag) database search, using the diffuse B-cell lymphoma (Dbl) homology (DH) domain query in the BLASTN system (Thiesen et al, 2000). It selectively activates RhoA and RhoB (Arthur et al, 2002). The present review provides a complete understanding of the intricacies of genetic association networks engaged in ARHGEF3-related pathologies, prompting advancements in potential treatment modalities via mechanistic investigations
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have