ARHGEF18

Rho GTPases are GTP binding proteins that regulate a wide spectrum of cellular functions. These cellular processes include cytoskeletal rearrangements, gene transcription, cell growth and motility. Activation of Rho GTPases is under the direct control of guanine nucleotide exchange factors (GEFs). The protein encoded by this gene is a guanine nucleotide exchange factor and belongs to the Rho GTPase GFE family. Family members share a common feature, a Dbl (DH) homology domain followed by a pleckstrin (PH) homology domain. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq]

Full Name

rho/rac guanine nucleotide exchange factor (GEF) 18

Function

Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. Also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950).

Biological Process

Actin cytoskeleton organization Source: MGI
G protein-coupled receptor signaling pathway Source: Reactome
Negative regulation of stress fiber assembly Source: ARUK-UCL
Positive regulation of apoptotic process Source: Reactome
Protein localization to cell-cell junction Source: ARUK-UCL
Regulation of cell shape Source: MGI
Regulation of Rho protein signal transduction Source: GO_Central
Regulation of small GTPase mediated signal transduction Source: Reactome
Small GTPase mediated signal transduction Source: MGI
Transforming growth factor beta receptor signaling pathway Source: Reactome

Cellular Location

Cytoskeleton; Cytoplasm; Cell membrane; Apical cell membrane. In unactivated eosinophils, distributed around the cell periphery in the perimembranous region (PubMed:29601110). In activated eosinophils, relocates to the tip of the nucleopod, a membrane structure formed during activation when the nucleus moves to one end of the cell, and is also concentrated in membrane protrusions at the opposite end of the cell (PubMed:29601110). Localizes to the apical cell membrane in epithelial cells (PubMed:22006950).

Involvement in disease

Retinitis pigmentosa 78 (RP78): A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP78 inheritance is autosomal recessive.