Porf-2 = Arhgap39 = Vilse: A Pivotal Role in Neurodevelopment, Learning and Memory

Small GTP-converting enzymes, GTPases, are essential for the efficient completion of many physiological and developmental processes. They are regulated by GTPase activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). Arhgap39, also known as preoptic regulatory factor-2 (Porf-2) or Vilse, a member of the Rho GAP group, was first identified in 1990 in the rat CNS. It has since been shown to regulate apoptosis, cell migration, neurogenesis, and cerebral and hippocampal dendritic spine morphology. It plays a pivotal role in neurodevelopment and learning and memory. Homologous or orthologous genes are found in more than 280 vertebrate and invertebrate species, suggesting preservation through evolution. Not surprisingly, loss of the Arhgap39/Porf-2 gene in mice manifests as an embryonic lethal condition. Although Arhgap39/Porf-2 is highly expressed in the brain, it is also widely distributed throughout the body, with potential additional roles in oncogenesis and morphogenesis. This review summarizes, for the first time, the known information about this gene under its various names, in addition to considering its transcripts and proteins. The majority of findings described have been made in rats, mice, humans, and fruit flies. This work surveys the known functions, functional mediators, variables modifying expression and upstream regulators of expression, and potential physiological and pathological roles of Arhgap39/Porf-2 in health and disease.