Article

IFT20 is required for opsin trafficking and photoreceptor outer segment development.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Molecular biology of the cell (Impact Factor: 5.98). 02/2011; 22(7):921-30. DOI: 10.1091/mbc.E10-09-0792
Source: PubMed

ABSTRACT The light-detecting outer segments of vertebrate photoreceptors are cilia. Like other cilia, all materials needed for assembly and maintenance are synthesized in the cell body and transported into the cilium. The highly elaborated nature of the outer segment and its high rate of turnover necessitate unusually high levels of transport into the cilium. In this work, we examine the role of the IFT20 subunit of the intraflagellar transport (IFT) particle in photoreceptor cells. IFT20 was deleted in developing cones by a cone-specific Cre and in mature rods and cones by a tamoxifen-activatable Cre. Loss of IFT20 during cone development leads to opsin accumulation in the inner segment even when the connecting cilium and outer segment are still intact. With time this causes cone cell degeneration. Similarly, deletion of IFT20 in mature rods causes rapid accumulation of rhodopsin in the cell body, where it is concentrated at the Golgi complex. We further show that IFT20, acting both as part of the IFT particle and independent of the particle, binds to rhodopsin and RG-opsin. Since IFT20 dynamically moves between the Golgi complex and the connecting cilium, the current work suggests that rhodopsin and opsins are cargo for IFT transport.

0 Bookmarks
 · 
129 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary cilia are essential cellular organelles projecting from the cell surface to sense and transduce developmental signaling. They are tiny but have complicated structures containing microtubule (MT)-based internal structures (the axoneme) and mother centriole formed basal body. Intraflagellar transport (Ift) operated by Ift proteins and motors are indispensable for cilia formation and function. Mutations in Ift proteins or Ift motors cause various human diseases, some of which have severe bone defects. Over the last few decades, major advances have occurred in understanding the roles of these proteins and cilia in bone development and remodeling by examining cilia/Ift protein-related human diseases and establishing mouse transgenic models. In this review, we describe current advances in the understanding of the cilia/Ift structure and function. We further summarize cilia/Ift-related human diseases and current mouse models with an emphasis on bone-related phenotypes, cilia morphology, and signaling pathways.
    Frontiers in Bioscience 01/2015; 20:515-55. DOI:10.2741/4323 · 4.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: As a cellular organelle, the cilium contains a unique protein composition [1, 2]. Entry of both membrane [3-5] and cytosolic [6-8] components is tightly regulated by gating mechanisms at the cilium base; however, the mechanistic details of ciliary gating are largely unknown. We previously proposed that entry of cytosolic components is regulated by mechanisms similar to those of nuclear transport and is dependent on nucleoporins (NUPs), which comprise a ciliary pore complex (CPC) [6, 9]. To investigate ciliary gating mechanisms, we developed a system to clog the pore by inhibiting NUP function via forced dimerization. We targeted NUP62, a component of the central channel of the nuclear pore complex (NPC) [10], for forced dimerization by tagging it with the homodimerizing Fv domain. As proof of principle, we show that forced dimerization of NUP62-Fv attenuated (1) active transport of BSA into the nuclear compartment and (2) the kinesin-2 motor KIF17 into the ciliary compartment. Using the pore-clogging technique, we find that forced dimerization of NUP62 attenuated the gated entry of cytosolic proteins but did not affect entry of membrane proteins or diffusional entry of small cytosolic proteins. We propose a model in which active transport of cytosolic proteins into both nuclear and ciliary compartments requires functional NUPs of the central pore, whereas lateral entry of membrane proteins utilizes a different mechanism that is likely specific to each organelle's limiting membrane.
    Current Biology 09/2014; 24(19). DOI:10.1016/j.cub.2014.08.012 · 9.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vertebrate hedgehog signaling is coordinated by the differential localization of the receptors patched-1 and Smoothened in the primary cilium. Cilia assembly is mediated by intraflagellar transport (IFT), and cilia defects disrupt hedgehog signaling, causing many structural birth defects. We generated Ift25 and Ift27 knockout mice and show that they have structural birth defects indicative of hedgehog signaling dysfunction. Surprisingly, ciliary assembly is not affected, but abnormal hedgehog signaling is observed in conjunction with ciliary accumulation of patched-1 and Smoothened. Similarly, Smoothened accumulates in cilia on cells mutated for BBSome components or the BBS binding protein/regulator Lztfl1. Interestingly, the BBSome and Lztfl1 accumulate to high levels in Ift27 mutant cilia. Because Lztfl1 mutant cells accumulate BBSome but not IFT27, it is likely that Lztfl1 functions downstream of IFT27 to couple the BBSome to the IFT particle for coordinated removal of patched-1 and Smoothened from cilia during hedgehog signaling. Copyright © 2014 Elsevier Inc. All rights reserved.
    Developmental Cell 11/2014; 31(3):279-90. DOI:10.1016/j.devcel.2014.09.011 · 10.37 Impact Factor

Full-text (2 Sources)

Download
36 Downloads
Available from
Jun 2, 2014