Arf GTPases and their GEFs and GAPS: Concepts and challenges

Elizabeth Sztul, Pei Wen Chen, James E. Casanova, Jacqueline Cherfils, Joel B. Dacks, David G. Lambright, Fang Jen S. Lee, Paul A. Randazzo, Lorraine C. Santy, Annette Schürmann, Ilka Wilhelmi, Marielle E. Yohe, Richard A. Kahn

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1249-1271
Number of pages23
JournalMolecular biology of the cell
Volume30
Issue number11
DOIs
StatePublished - Jan 1 2019

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GTP Phosphohydrolases
Proteins
GTPase-Activating Proteins
Guanine Nucleotide Exchange Factors
Pliability
Cell Biology
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Sztul, E., Chen, P. W., Casanova, J. E., Cherfils, J., Dacks, J. B., Lambright, D. G., ... Kahn, R. A. (2019). Arf GTPases and their GEFs and GAPS: Concepts and challenges. Molecular biology of the cell, 30(11), 1249-1271. https://doi.org/10.1091/mbc.E18-12-0820
Sztul, Elizabeth ; Chen, Pei Wen ; Casanova, James E. ; Cherfils, Jacqueline ; Dacks, Joel B. ; Lambright, David G. ; Lee, Fang Jen S. ; Randazzo, Paul A. ; Santy, Lorraine C. ; Schürmann, Annette ; Wilhelmi, Ilka ; Yohe, Marielle E. ; Kahn, Richard A. / Arf GTPases and their GEFs and GAPS : Concepts and challenges. In: Molecular biology of the cell. 2019 ; Vol. 30, No. 11. pp. 1249-1271.
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Sztul, E, Chen, PW, Casanova, JE, Cherfils, J, Dacks, JB, Lambright, DG, Lee, FJS, Randazzo, PA, Santy, LC, Schürmann, A, Wilhelmi, I, Yohe, ME & Kahn, RA 2019, 'Arf GTPases and their GEFs and GAPS: Concepts and challenges', Molecular biology of the cell, vol. 30, no. 11, pp. 1249-1271. https://doi.org/10.1091/mbc.E18-12-0820

Arf GTPases and their GEFs and GAPS : Concepts and challenges. / Sztul, Elizabeth; Chen, Pei Wen; Casanova, James E.; Cherfils, Jacqueline; Dacks, Joel B.; Lambright, David G.; Lee, Fang Jen S.; Randazzo, Paul A.; Santy, Lorraine C.; Schürmann, Annette; Wilhelmi, Ilka; Yohe, Marielle E.; Kahn, Richard A.

In: Molecular biology of the cell, Vol. 30, No. 11, 01.01.2019, p. 1249-1271.

Research output: Contribution to journalReview article

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T1 - Arf GTPases and their GEFs and GAPS

T2 - Concepts and challenges

AU - Sztul, Elizabeth

AU - Chen, Pei Wen

AU - Casanova, James E.

AU - Cherfils, Jacqueline

AU - Dacks, Joel B.

AU - Lambright, David G.

AU - Lee, Fang Jen S.

AU - Randazzo, Paul A.

AU - Santy, Lorraine C.

AU - Schürmann, Annette

AU - Wilhelmi, Ilka

AU - Yohe, Marielle E.

AU - Kahn, Richard A.

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N2 - 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.

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Sztul E, Chen PW, Casanova JE, Cherfils J, Dacks JB, Lambright DG et al. Arf GTPases and their GEFs and GAPS: Concepts and challenges. Molecular biology of the cell. 2019 Jan 1;30(11):1249-1271. https://doi.org/10.1091/mbc.E18-12-0820