The Rac3 GTPase in Neuronal Development, Neurodevelopmental Disorders, and Cancer

Abstract

Rho family small guanosine triphosphatases (GTPases) are important regulators of the cytoskeleton, and are critical in many aspects of cellular and developmental biology, as well as in pathological processes such as intellectual disability and cancer. Of the three members of the family, Rac3 has a more restricted expression in normal tissues compared to the ubiquitous member of the family, Rac1. The Rac3 polypeptide is highly similar to Rac1, and orthologues of the gene for Rac3 have been found only in vertebrates, indicating the late appearance of this gene during evolution. Increasing evidence over the past few years indicates that Rac3 plays an important role in neuronal development and in tumor progression, with specificities that distinguish the functions of Rac3 from the established functions of Rac1 in these processes. Here, results highlighting the importance of Rac3 in distinct aspects of neuronal development and tumor cell biology are presented, in support of the non-redundant role of different members of the two Rac GTPases in physiological and pathological processes.

Metabolic labeling with an alkyne probe reveals similarities and differences in the prenylomes of several brain-derived cell lines and primary cells

“…Rac3, a member of the Rho family GTPases, is also abundantly expressed in neurons. Rac3 plays essential roles in neuronal development and related disorders 63 . The presence of the C-terminal prenylation site of Rac3 is specifically required for the maturation of neurons in culture.…”

Pathophysiological Mechanisms in Neurodevelopmental Disorders Caused by Rac GTPases Dysregulation: What’s behind Neuro-RACopathies

“…Several studies have provided scientific evidence in favor of a critical role for RHO family GTPases in neuronal development, also entailing the pathogenic implications of a disrupted GTPase signaling in the pathophysiology of neurodevelopmental disorders (NDDs) [ 3 , 20 , 21 , 22 , 23 ]. Rac1 and Rac2 were the first members of the Rac subfamily to be characterized, with Rac1 being identified as a 21,450 dalton protein substrate for ADP-ribosylation by the C3 component of botulinum toxin [ 24 ].…”

“…Rac1 is ubiquitously expressed from the early embryonic stage [ 16 ]. A high sequence similarity (88–92% identity) is typical of the Rac subfamily of RHO GTPases, which mostly diverge in the last 10 carboxy-terminal residues [ 21 ]. Two Rac1 transcripts (1.2 and 2.5 kb) are ubiquitously expressed in a tissue-specific manner, based on two competing alternative polyadenylation sites [ 25 ].…”

MicroRNA Regulation of the Small Rho GTPase Regulators—Complexities and Opportunities in Targeting Cancer Metastasis

“…Involved in synaptic potentiation through regulating the actin cytoskeletal dynamics; Primarily expressed in the neurons of ganglia and the central nervous system. [37,38] RHOA Involved in the regulation of cell adhesion and migration; Responsible for providing contractile force in cell migration through the formation of stress fibers and focal adhesions; Localized to the cytoplasm and to a certain degree the plasma membrane. [39,40] RHOB Transducer involved in actin organization, cell migration, membrane and endosome trafficking, proliferation, DNA repair, and apoptosis; Thought to be an inhibitor of cancer progression; Localized to the endosomal membrane.…”