Article
- The EMBO Journal (2009) 28, 183 - 192
- doi:10.1038/emboj.2008.267
Published online: 15 January 2009
Subject Categories:
Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4
Jana Mazelova1, Lisa Astuto-Gribble1, Hiroki Inoue2, Beatrice M Tam3, Eric Schonteich4, Rytis Prekeris4, Orson L Moritz3, Paul A Randazzo2 and Dusanka Deretic1,5
- Division of Ophthalmology, Department of Surgery, University of New Mexico, Albuquerque, NM, USA
- Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
- Department of Cell and Developmental Biology, University of Colorado Health Sciences Center, Aurora, CO, USA
- Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, USA
Correspondence to:
Dusanka Deretic, Division of Ophthalmology, Department of Surgery, University of New Mexico School of Medicine, Basic Medical Sciences Building, Room 377, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA. Tel.: +1 505 272 4968; Fax: +1 505 272 6029; E-mail: dderetic@salud.unm.edu
Received 5 May 2008; Accepted 26 November 2008
Abstract
Dysfunctions of primary cilia and cilia-derived sensory organelles underlie a multitude of human disorders, including retinal degeneration, yet membrane targeting to the cilium remains poorly understood. Here, we show that the newly identified ciliary targeting VxPx motif present in rhodopsin binds the small GTPase Arf4 and regulates its association with the trans-Golgi network (TGN), which is the site of assembly and function of a ciliary targeting complex. This complex is comprised of two small GTPases, Arf4 and Rab11, the Rab11/Arf effector FIP3, and the Arf GTPase-activating protein ASAP1. ASAP1 mediates GTP hydrolysis on Arf4 and functions as an Arf4 effector that regulates budding of post-TGN carriers, along with FIP3 and Rab11. The Arf4 mutant I46D, impaired in ASAP1-mediated GTP hydrolysis, causes aberrant rhodopsin trafficking and cytoskeletal and morphological defects resulting in retinal degeneration in transgenic animals. As the VxPx motif is present in other ciliary membrane proteins, the Arf4-based targeting complex is most likely a part of conserved machinery involved in the selection and packaging of the cargo destined for delivery to the cilium.
Keywords:
- Arfs,
- cilium,
- Rabs,
- rhodopsin,
- trafficking
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Nature Reviews Molecular Cell Biology Review (01 Nov 2002)
Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease?
Nature Reviews Genetics Review (01 Dec 2005)
RESEARCH
Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia
The EMBO Journal Article (21 Dec 2005)
The EMBO Journal Article (01 Apr 1997)
Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo
Nature Structural & Molecular Biology Article (01 Oct 2005)
