Arf GAPs as Regulators of the Actin Cytoskeleton—An Update

Abstract

Arf GTPase-activating proteins (Arf GAPs) control the activity of ADP-ribosylation factors (Arfs) by inducing GTP hydrolysis and participate in a diverse array of cellular functions both through mechanisms that are dependent on and independent of their Arf GAP activity. A number of these functions hinge on the remodeling of actin filaments. Accordingly, some of the effects exerted by Arf GAPs involve proteins known to engage in regulation of the actin dynamics and architecture, such as Rho family proteins and nonmuscle myosin 2. Circular dorsal ruffles (CDRs), podosomes, invadopodia, lamellipodia, stress fibers and focal adhesions are among the actin-based structures regulated by Arf GAPs. Arf GAPs are thus important actors in broad functions like adhesion and motility, as well as the specialized functions of bone resorption, neurite outgrowth, and pathogen internalization by immune cells. Arf GAPs, with their multiple protein-protein interactions, membrane-binding domains and sites for post-translational modification, are good candidates for linking the changes in actin to the membrane. The findings discussed depict a family of proteins with a critical role in regulating actin dynamics to enable proper cell function.

The effect of lncRNA‐ARAP1‐AS2/ARAP1 on high glucose‐induced cytoskeleton rearrangement and epithelial–mesenchymal transition in human renal tubular epithelial cells

“…ARAP1 is a member of the ARAP family. ARAP is a point of convergence for Arf and Rho signaling and plays an important role in cytoskeleton rearrangement and Golgi apparatus remodeling (Santy, & Casanova, 2002; Tanna, Goss, Ludwig, & Chen, 2019). As a member of the ARAP family, ARAP1 is also involved in the endocytic trafficking of membrane receptors, including epidermal growth factor receptor (EGFR; Yoon, Kales, Luo, Lipkowitz, & Randazzo, 2011; Yoon, Lee, & Randazzo, 2008) and tumor necrosis factor‐related apoptosis‐inducing ligand receptor 1 (TRAIL‐R1; Šímová, Klíma, Cermak, Šourková, & Anděra, 2008).…”

The ArfGAP ASAP1 Controls Actin Stress Fiber Organization via Its N-BAR Domain

“…In humans, 31 genes encode proteins containing an ArfGAP (ADP ribosylation factor GTPase-activating protein) domain, which stimulates the hydrolysis of the GTP nucleotide by the Arf (ADP-ribosylation factor) GTPases (Kahn et al., 2008). The ArfGAP family has been shown to regulate actin-based structures (reviewed in Tanna et al, 2019). ASAP and ACAP family members are unique in that they contain an N-terminal BAR domain.…”

The BAR domain of the Arf GTPase-activating protein ASAP1 directly binds actin filaments

“…Further, it showed that reduced ASAP1 expression results in the depletion of ventral stress fibers, whereas increased ASAP1 expression results in more pronounced stress fibers and the appearance of cellular projections. Our cellular studies focus on cellular projections extending from the cell periphery in more detail, as the effect of ASAP1 expression on this type of structure has not been characterized extensively (5,12). Moreover, the results from both studies suggest that the ASAP1 N-BAR domain is under autoinhibitory regulation, as has previously been described for other BAR domain proteins, such as PICK1, syndapin, and FCHSD2 (45,46).…”

“…ASAP1, an Arf GTPase-activating protein (Arf GAP), is a direct mediator of the membrane-associated actin cytoskeleton and is critical for the regulation of circular dorsal ruffles, focal adhesions, invadopodia, and podosomes (5,(9)(10)(11)(12). Unifying features of these cytoskeletal structures are thick actin bundles that assemble and disassemble in a strictly controlled manner.…”