ARF family GTPases with links to cilia.

American Journal of Physiology. Cell Physiology
Skylar FisherElizabeth Sztul

Abstract

The ADP-ribosylation factor (ARF) superfamily of regulatory GTPases, including both the ARF and ARF-like (ARL) proteins, control a multitude of cellular functions, including aspects of vesicular traffic, lipid metabolism, mitochondrial architecture, the assembly and dynamics of the microtubule and actin cytoskeletons, and other pathways in cell biology. Considering their general utility, it is perhaps not surprising that increasingly ARF/ARLs have been found in connection to primary cilia. Here, we critically evaluate the current knowledge of the roles four ARF/ARLs (ARF4, ARL3, ARL6, ARL13B) play in cilia and highlight key missing information that would help move our understanding forward. Importantly, these GTPases are themselves regulated by guanine nucleotide exchange factors (GEFs) that activate them and by GTPase-activating proteins (GAPs) that act as both effectors and terminators of signaling. We believe that the identification of the GEFs and GAPs and better models of the actions of these GTPases and their regulators will provide a much deeper understanding and appreciation of the mechanisms that underly ciliary functions and the causes of a number of human ciliopathies.

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Citations

Jul 16, 2020·American Journal of Physiology. Cell Physiology·Kirk L Hamilton
Feb 18, 2021·Molecular Biology of the Cell·Rachel E TurnRichard A Kahn
Jun 23, 2021·Journal of Cell Science·Magdalena Cardenas-RodriguezIain A Drummond
Jul 12, 2021·Genome Biology and Evolution·Romana VargováMarek Eliáš

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Methods Mentioned

BETA
GTPase
GTPases
nucleotide exchange
nucleotide
Transgenic
transfection
biosensors
two-hybrid

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