ARF GTPases and their GEFs and GAPs: concepts and challenges

Elizabeth Sztul (1) , Pei-Wen Chen (2) , James Casanova (3) , Jacqueline Cherfils (4) , Joel B Dacks (5) , David Lambright (6) , Fang-Jen Lee (7) , Paul Randazzo (8) , Lorraine Santy (9) , Annette Schürmann (10) , Ilka Wilhelmi (10) , Marielle Yohe (11) , Richard A. Kahn (12)

1 UAB - University of Alabama at Birmingham [ Birmingham]
2 Williams College [Williamstown]
3 University of Virginia
4 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée
5 University of Alberta
6 UMASS - University of Massachusetts Medical School [Worcester]
7 NTU - National Taïwan University
8 NIH - National Institutes of Health [Bethesda, MD, USA]
9 Penn State - Pennsylvania State University
10 German Institute of Human Nutrition (DIfE)
11 NCI-NIH - National Cancer Institute [Bethesda]
12 Emory University School of Medicine

Detailed structural, biochemical, cell biological, and genetic studies of any gene/protein are required to develop models of its actions in cells. Studying a protein family in the aggregate yields additional information, as one can include analyses of their coevolution, acquisition or loss of functionalities, structural pliability, and the emergence of shared or variations in molecular mechanisms. An even richer understanding of cell biology can be achieved through evaluating functionally linked protein families. In this review, we summarize current knowledge of three protein families: the ARF GTPases, the guanine nucleotide exchange factors (ARF GEFs) that activate them, and the GTPase-activating proteins (ARF GAPs) that have the ability to both propagate and terminate signaling. However, despite decades of scrutiny, our understanding of how these essential proteins function in cells remains fragmentary. We believe that the inherent complexity of ARF signaling and its regulation by GEFs and GAPs will require the concerted effort of many laboratories working together, ideally within a consortium to optimally pool information and resources. The collaborative study of these three functionally connected families (≥70 mammalian genes) will yield transformative insights into regulation of cell signaling.

Domaines: Biochimie, Biologie Moléculaire

Elizabeth Sztul, Pei-Wen Chen, James Casanova, Jacqueline Cherfils, Joel B Dacks, et al.. ARF GTPases and their GEFs and GAPs: concepts and challenges. Molecular Biology of the Cell, 2019, 30 (11), pp.1249-1271. ⟨10.1091/mbc.E18-12-0820⟩. ⟨hal-02363294⟩