AGAPs

AGAPs are a family of ARF GTPase-activating proteins (ARF GAPs) that regulate members of the ARF family of small GTPases. By stimulating the GTPase activity of ARFs, they help switch ARFs from the active GTP-bound state to the inactive GDP-bound state, thereby modulating vesicle formation, trafficking between the Golgi and endosomes, and dynamics of the actin cytoskeleton. Through these actions, AGAPs influence processes such as endocytosis, receptor trafficking, and membrane remodeling.

Most AGAP proteins share the ARF GAP catalytic domain responsible for GTPase activation. Many family members also contain additional domains, such as pleckstrin homology (PH) domains that bind phosphoinositides and determine membrane localization, as well as ankyrin repeats or other motifs that mediate protein–protein interactions. The combination of catalytic and targeting domains allows AGAPs to act at specific membranes and in particular signaling contexts.

AGAPs are found across eukaryotes, with several paralogs in vertebrates. In humans, multiple AGAP genes (for example AGAP1, AGAP2, and AGAP3) encode distinct proteins with tissue-specific expression and subcellular localization. Functionally, AGAPs have been linked to neuronal development and synaptic function, and to regulation of receptor trafficking and cell migration in some cancer models. Subcellular localization often includes the Golgi apparatus, endosomes, and dendrites, consistent with roles in vesicular trafficking.

Research on AGAPs continues to clarify their specific ARF substrates, regulatory mechanisms, and involvement in disease. They are subjects of interest in cell biology and neuroscience, both as models of ARF signaling and as potential targets for modulating trafficking pathways.