Conversion of anterograde into retrograde trains is an intrinsic property of intraflagellar transport.

First Authors Adrian Pascal Nievergelt
Authors Adrian Pascal Nievergelt, Ilia Zykov, Dennis R Diener, Aditya Chhatre, Tim-Oliver Buchholz, Markus Delling, Stefan Diez, Florian Jug, Luděk Štěpánek, Gaia Pigino
Corresponding Authors Luděk Štěpánek, Gaia Pigino
Last Authors Gaia Pigino
Journal Name Current biology : CB (Curr Biol)
Volume 32
Issue 18
Page Range 4071-4078
Open Access true
Print Publication Date 2022-09-26
Online Publication Date
Abstract Cilia or eukaryotic flagella are microtubule-based organelles found across the eukaryotic tree of life. Their very high aspect ratio and crowded interior are unfavorable to diffusive transport of most components required for their assembly and maintenance. Instead, a system of intraflagellar transport (IFT) trains moves cargo rapidly up and down the cilium (Figure 1A).1-3 Anterograde IFT, from the cell body to the ciliary tip, is driven by kinesin-II motors, whereas retrograde IFT is powered by cytoplasmic dynein-1b motors.4 Both motors are associated with long chains of IFT protein complexes, known as IFT trains, and their cargoes.5-8 The conversion from anterograde to retrograde motility at the ciliary tip involves (1) the dissociation of kinesin motors from trains,9 (2) a fundamental restructuring of the train from the anterograde to the retrograde architecture,8,10,11 (3) the unloading and reloading of cargo,2 and (4) the activation of the dynein motors.8,12 A prominent hypothesis is that there is dedicated calcium-dependent protein-based machinery at the ciliary tip to mediate these processes.4,13 However, the mechanisms of IFT turnaround have remained elusive. In this study, we use mechanical and chemical methods to block IFT at intermediate positions along the cilia of the green algae Chlamydomonas reinhardtii, in normal and calcium-depleted conditions. We show that IFT turnaround, kinesin dissociation, and dynein-1b activation can consistently be induced at arbitrary distances from the ciliary tip, with no stationary tip machinery being required. Instead, we demonstrate that the anterograde-to-retrograde conversion is a calcium-independent intrinsic ability of IFT.
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Affiliated With CSBD, Diez, Jug, Pigino, Postdoc first author, Postdoc first male, Postdocs
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Acknowledged Services EM Facility, Protein Expression, Light Microscopy Facility
Publication Status Published
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DOI 10.1016/j.cub.2022.07.033
PubMed ID 35926510
WebOfScience Link WOS:000871825200006
Alternative Full Text URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9521741/
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Created By thuem
Added Date 2022-08-09
Last Edited By thuem
Last Edited Date 2022-11-24 16:23:28.718
Library ID 8429
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Grant ID 1. 819826; 2. PI1218/3-1
Funding Programme Horizon 2020 (H2020)
Funding Organisation 1.European Commission (EC); 2. DFG