Abstract
As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo- and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.
Highlights
Intracellular membrane trafficking along endocytic and exocytic pathways is essential for the transport of proteins and membranes in all eukaryotic cells and contributes to the maintenance of cellular homeostasis
As opposed to Ras GTPases, which are hyperactivated in approximately a quarter of all human cancers [144], dysregulation of Rho GTPase signaling has mainly been attributed to Rho GTPase overexpression or altered guanine nucleotide exchange factors (GEFs) or GTPase-activating proteins (GAPs) levels
Our knowledge of the regulation of membrane trafficking through Rho GTPases has vastly increased in the past years
Summary
Intracellular membrane trafficking along endocytic and exocytic pathways is essential for the transport of proteins and membranes in all eukaryotic cells and contributes to the maintenance of cellular homeostasis Transport carriers, such as vesicles and tubules that form and bud from donor membranes are transported along microtubules and actin filaments and fuse with their target membrane. GTPase-activating proteins by guanine nucleotide exchange factors (GEFs) that promote the formation of the active GTP-bound (GAPs) catalyze the intrinsic GTPase activity and promote the formation of inactive GDP-bound Rho. form through exchanging GDP for GTP. In the case of atypical Rho. GDP/GTP cycling, atypical Rho GTPases are regulated by other mechanisms that occur in particular at GTPases, GTP is usually constitutively bound, either because these Rho GTPases possess high the transcriptional and post-translational level [7]. Activity or have substitutions in their GTPase domain that prevent GTP hydrolysis
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