Small GTPases: Structure, biological function and its interaction with nanoparticles

Abstract

Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells. It plays an important role in cytoskeletal reorganization, cell polarity, cell cycle progression, gene expression and many other significant events in cells, such as the interaction with foreign particles. Therefore, it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay, since more and more nanomedicine are supposed to be used in biomedical field. However, there is no review in this aspect. This review summarizes the small GTPases in terms of the structure, biological function and its interaction with nanoparticles. We briefly introduced the various nanoparticles such as gold/silver nanoparticles, SWCNT, polymeric micelles and other nano delivery systems that interacted with different GTPases. These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study. This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction. It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.

Keywords: Nanoparticles; Rab; Ras; Rho; Small GTPase.

Graphical abstract

Fig. 1

(A) Schematic diagram of the small GTPase protein sequence. (B) Regulation of small GTPase activity. GTPases cycle between their GTP-bound active and GDP-bound inactive form. They are activated by guanine-nucleotide exchange factors (GEFs), which remove GDP, thus enabling excess cellular GTP to bind. The binding of active GTPase to downstream effector proteins elicits cell responses. GTPase-activating proteins (GAPs), which increase the GTPase activity, are the off-switch. Inactive Rac is sequestered in the cytosol by guanine-nucleotide dissociation inhibitors (GDIs). Reproduced with permission from . Copyright 2018 John Wiley & Sons, Inc.

Fig. 2

Overview of Rab GTPases on the endocytic pathway. Rab GTPases function in internalization and transport to degradation, as well as recycling to the plasma membrane and the Golgi. The numbers in the figure indicate other kinds of Rab GTPases, for example, 14 represented of Rab14. Reproduced with permission from . Copyright 2014 Cold Spring Harbor Laboratory Press.

Fig. 3

(A) Scheme of nanoparticles biofunctionalized nerve implants, are taken up by cells and enable neurite out growth. (B) Neuronal response to nanoparticles by RhoA protein reduction . Copyright (2010), American Chemical Society. (C) Staining of filamentous actin in the AgNP-treated was stronger than that of the control and AgNO₃-treated cells . Copyright (2014), Dovepress Ltd. (D) Fibroblasts on RGD-gold squares smaller than 1 mm show altered morphology. Reproduced with permission from . Copyright 2011 Public Library of Science.

Fig. 4

Schematic representation of the intracellular trafficking network of MSNs. Reproduced with permission from . Copyright 2017 American Chemical Society.