The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic

• Type of Material: Article
• Authors: Rachel E Turn, Emory University; Yihan Hu, Emory University; Skylar Dewees, Emory University; Narra Devi, Emory University; Michael P East, University of North Carolina; Katherine R Hardin, Emory University; Tala Khatib, Emory University; Joshua Linnert, Johannes Gutenberg University of Mainz; Uwe Wolfrum, Johannes Gutenberg University of Mainz; Michael J Lim, University of Virginia; James E Casanova, University of Virginia; Tamara Caspary, Emory University; Richard Kahn, Emory University
• Language: English
• Date: 2022-02-01
• Publisher: AMER SOC CELL BIOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Turn, Hu, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1091/mbc.E21-09-0443
• Title of Journal or Parent Work: MOLECULAR BIOLOGY OF THE CELL
• Volume: 33
• Issue: 2
• Start Page: ar13
• End Page: ar13
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health: R35GM122568 to R.A.K., R35GM122549 to T.C., R01GM127361 to J.E.C.; 1F31CA236493-02 to R.E.T., and 1F31HD096815-03 to S.I.D.; the Foundation Fighting Blindness (FFB PPA-0717-0719-RAD) to U.W.; the German Research Council/DFG in the framework of SPP SPP2127—Gene and Cell based therapies to counteract neuro-retinal degeneration WO548/9-1 to U.W.; and the joint training program between the Emory University School of Medicine and the Xiangya School of Medicine, Central South University (Y.H.).
• Keywords: GTPASE; INOSITOL-POLYPHOSPHATE 5-PHOSPHATASE; MEMBRANE; Science & Technology; IFT-A COMPLEX; INPP5E; Life Sciences & Biomedicine; Cell Biology; ARL13B; BINDING; TRANSPORT; CANDIDATE GENE; MOTHER CENTRIOLE
• Research Categories: Health Sciences, Immunology; Biology, Cell; Biology, Microbiology; Chemistry, Biochemistry

Abstract

ELMODs are a family of three mammalian paralogues that display GTPase-activating protein (GAP) activity toward a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogues ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regulators and compare them to those of ELMOD2, allowing the determination of functional redundancy among the family members. We found strong similarities in phenotypes resulting from deletion of either Elmod1 or Elmod3 and marked differences from those arising in Elmod2 deletion lines. Deletion of either Elmod1 or Elmod3 results in the decreased ability of cells to form primary cilia, loss of a subset of proteins from cilia, and accumulation of some ciliary proteins at the Golgi, predicted to result from compromised traffic from the Golgi to cilia. These phenotypes are reversed upon activating mutant expression of either ARL3 or ARL16, linking their roles to ELMOD1/3 actions.