Roles for ELMOD2 and Rootletin in ciliogenesis

• Type of Material: Article
• Authors: Rachel E Turn, Emory University; Joshua Linnert, Johannes Gutenberg University of Mainz; Eduardo D Gigante, Emory University; Uwe Wolfrum, Johannes Gutenberg University of Mainz; Tamara Caspary, Emory University; Richard Kahn, Emory University
• Language: English
• Date: 2021-04-15
• Publisher: AMER SOC CELL BIOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Turn 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-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1091/mbc.E20-10-0635
• Title of Journal or Parent Work: MOLECULAR BIOLOGY OF THE CELL
• Volume: 32
• Issue: 8
• Start Page: 800
• End Page: 822
• Grant/Funding Information: This work was supported by National Institutes of Health grants R35GM122568 (R.A.K.), T32GM8367 (R.E.T.; ORCID 0000-0001-5389-4560), F31CA236493-02 (R.E.T.), T32NS090650 (E.D.G.; ORCID 0000-0002-1486-5377), F31NS106755 (E.D.G.), and R35GM122549 (T. C.; ORCID 0000-0002-6579-7589) and by Foundation Fighting Blindness (FFB) PPA-0717-0719-RAD (U. W.).
• Keywords: CANDIDATE GENE; PHOTORECEPTOR CELLS; CILIARY; GTPASE-ACTIVATING PROTEIN; PRIMARY CILIUM; F-ACTIN; Life Sciences & Biomedicine; COUPLED RECEPTOR GPR161; VESICLE TRANSPORT; INTRAFLAGELLAR TRANSPORT; ARF FAMILY; Science & Technology; Cell Biology
• Research Categories: Chemistry, Biochemistry

Abstract

ELMOD2 is a GTPase-activating protein with uniquely broad specificity for ARF family GTPases. We previously showed that it acts with ARL2 in mitochondrial fusion and microtubule stability and with ARF6 during cytokinesis. Mouse embryonic fibroblasts deleted for ELMOD2 also displayed changes in cilia-related processes including increased ciliation, multiciliation, ciliary morphology, ciliary signaling, centrin accumulation inside cilia, and loss of rootlets at centrosomes with loss of centrosome cohesion. Increasing ARL2 activity or overexpressing Rootletin reversed these defects, revealing close functional links between the three proteins. This was further supported by the findings that deletion of Rootletin yielded similar phenotypes, which were rescued upon increasing ARL2 activity but not ELMOD2 overexpression. Thus, we propose that ARL2, ELMOD2, and Rootletin all act in a common pathway that suppresses spurious ciliation and maintains centrosome cohesion. Screening a number of markers of steps in the ciliation pathway supports a model in which ELMOD2, Rootletin, and ARL2 act downstream of TTBK2 and upstream of CP110 to prevent spurious release of CP110 and to regulate ciliary vesicle docking. These data thus provide evidence supporting roles for ELMOD2, Rootletin, and ARL2 in the regulation of ciliary licensing.