Ancient complement and lineage-specific evolution of the Sec7 ARF GEF proteins in eukaryotes

• Type of Material: Article
• Authors: Shweta V. Pipaliya, University of Alberta; Alexander Schlacht, University of Alberta; Christen M. Klinger, University of Alberta; Richard A Kahn, Emory University; Joel Dacks, University of Alberta
• Language: English
• Date: 2019-07-15
• Publisher: American Society for Cell Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Pipaliya et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1091/mbc.E19-01-0073
• Title of Journal or Parent Work: Molecular Biology of the Cell
• ISSN: 1059-1524
• Volume: 30
• Issue: 15
• Start Page: 1846
• End Page: 1863
• Grant/Funding Information: This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada (RES0021028, RES0043758, RES0046091) to J.B.D.; and the National Institute of General Medical Sciences (R35 GM122568) to R.A.K.; S.V.P. is funded by a Frederick Banting and Charles Best Canada Graduate Scholarship (Master’s).; A.S. was funded by the NSERC Postgraduate Scholarship-Doctoral Program, while C.M.K. is funded by a Canada Vanier Graduate Scholarship.
• Keywords: STRUCTURAL DETERMINANTS; DOMAIN; FAMILY; GTPASES; MEMBRANE-TRAFFICKING; Life Sciences & Biomedicine; Cell Biology; ACTIVATION; TRANS-GOLGI NETWORK; BREFELDIN-A; ADAPTER PROTEINS; Science & Technology; NUCLEOTIDE EXCHANGE FACTOR
• Research Categories: Biology, Cell; Health Sciences, Medicine and Surgery; Chemistry, Biochemistry

Abstract

Guanine nucleotide exchange factors (GEFs) are the initiators of signaling by every regulatory GTPase, which in turn act to regulate a wide array of essential cellular processes. To date, each family of GTPases is activated by distinct families of GEFs. Bidirectional membrane trafficking is regulated by ADP-ribosylation factor (ARF) GTPases and the development throughout eukaryotic evolution of increasingly complex systems of such traffic required the acquisition of a functionally diverse cohort of ARF GEFs to control it. We performed phylogenetic analyses of ARF GEFs in eukaryotes, defined by the presence of the Sec7 domain, and found three subfamilies (BIG, GBF1, and cytohesins) to have been present in the ancestor of all eukaryotes. The four other subfamilies (EFA6/PSD, IQSEC7/BRAG, FBX8, and TBS) are opisthokont, holozoan, metazoan, and alveolate/haptophyte specific, respectively, and each is derived from cytohesins. We also identified a cytohesin-derived subfamily, termed ankyrin repeat-containing cytohesin, that independently evolved in amoebozoans and members of the SAR and haptophyte clades. Building on evolutionary data for the ARF family GTPases and their GTPase-activating proteins allowed the generation of hypotheses about ARF GEF protein function(s) as well as a better understanding of the origins and evolution of cellular complexity in eukaryotes.