ADP-Ribosylation Factor Family of Small GTP-Binding Proteins: Their Membrane Recruitment, Activation, Crosstalk and Functions.

Tiantian Li,Yusong Guo

doi:10.3389/fcell.2022.813353

Abstract

Members of the ADP-ribosylation factor (ARF) family of guanine-nucleotide binding proteins play critical roles in various cellular processes, especially in regulating the secretory, and endocytic pathways. The fidelity of intracellular vesicular trafficking depends on proper activations and precise subcellular distributions of ARF family proteins regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Here we review recent progress in understanding the membrane recruitment, activation, crosstalk, and functions of ARF family proteins.

Highlights

The small G proteins, refer to the low molecular weight guanine-nucleotide-binding proteins, are responsible for the spatial and temporal regulation of many intracellular processes
Arfs can switch between a GTP-bound active state and a GDP-bound inactive state, catalyzed by Arf family guanine nucleotideexchange factors (Arf guanine nucleotide exchange factors (GEFs)) and guanine nucleotideactivating proteins (Arf GTPaseactivating proteins (GAPs)), respectively
Replacing Arf-related protein 1 (Arfrp1) N-terminal region with Arl14 N-terminal region causes the localization of the chimeric protein to switch from the Golgi to the plasma membrane. These results suggest that Arfrp1 N-terminal region or Arl14 N-terminal region is sufficient to determine their spatial localization, which may override the spatial determinants provided by the interaction between Arf GEFs and specific ADP-ribosylation factor (ARF) family proteins (Yang et al, 2020)

Summary

INTRODUCTION

The small G proteins, refer to the low molecular weight guanine-nucleotide-binding proteins, are responsible for the spatial and temporal regulation of many intracellular processes These proteins are classified into several major families including Arf, Rab, Ran, Ras, Rad, Rap, and Rho (Liu et al, 2017). Utilizing genome sequencing, a wider range of small G proteins were classified as members in the ARF family, including the Arf-like (Arl) proteins, Sar, and Arf-related protein 1 (Arfrp1) (Pasqualato et al, 2002; Kahn et al, 2006). These proteins lack ADP-ribosylation activity but share the structural features with Arfs. Arfs have similar structural organizations, composed of highly conserved effector regions including the switch 1 and switch 2 region, the inter-switch region, and the amphipathic helix at

Mechanistic Insights Into Arf Proteins

MEMBRANE RECRUITMENT AND ACTIVATION OF ARF FAMILY PROTEINS

EXPERIMENTAL APPROACHES TO STUDY THE FUNCTIONAL ROLES OF ARF FAMILY PROTEINS

FUTURE PERSPECTIVES

AUTHOR CONTRIBUTIONS