Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Cells

卷:10

Miguel Ángel del Pozo¹  Miguel Sánchez-Álvarez¹  Inmaculada Navarro-Lérida² 

[1] Centro Nacional de Investigaciones Cardiovasculares (CNIC), Mechanoadaptation and Caveolae Biology Lab., Cell and Developmental Biology Area, 28029 Madrid, Spain;

[2] Centro de Biología Molecular “Severo Ochoa”, Department of Molecular Biology, Campus de Cantoblanco, School of Sciences, Universidad Autónoma de Madrid, 28049 Madrid, Spain;

关键词: Rho GTPases;    post-translational modifications (PTMs);    subcellular compartmentalization;    plasma membrane (PM);    cytoskeleton;    nucleus;   

DOI  :  10.3390/cells10081990

来源: DOAJ

【 摘 要 】

Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

【 授权许可】

Unknown