Mechanisms of Regulation in Intraflagellar Transport

Wouter Mul; Aniruddha Mitra; Erwin J.G. Peterman

doi:10.3390/cells11172737

Mechanisms of Regulation in Intraflagellar Transport

Wouter Mul
, Aniruddha Mitra^*
, Erwin J.G. Peterman

^*Corresponding author for this work

Research output: Contribution to Journal › Review article › Academic › peer-review

Abstract

Cilia are eukaryotic organelles essential for movement, signaling or sensing. Primary cilia act as antennae to sense a cell’s environment and are involved in a wide range of signaling pathways essential for development. Motile cilia drive cell locomotion or liquid flow around the cell. Proper functioning of both types of cilia requires a highly orchestrated bi-directional transport system, intraflagellar transport (IFT), which is driven by motor proteins, kinesin-2 and IFT dynein. In this review, we explore how IFT is regulated in cilia, focusing from three different perspectives on the issue. First, we reflect on how the motor track, the microtubule-based axoneme, affects IFT. Second, we focus on the motor proteins, considering the role motor action, cooperation and motor-train interaction plays in the regulation of IFT. Third, we discuss the role of kinases in the regulation of the motor proteins. Our goal is to provide mechanistic insights in IFT regulation in cilia and to suggest directions of future research.

Original language	English
Article number	2737
Pages (from-to)	1-25
Number of pages	25
Journal	Cells
Volume	11
Issue number	17
DOIs	https://doi.org/10.3390/cells11172737
Publication status	Published - 1 Sept 2022

Bibliographical note

Special Issue: Primary Cilia in the Nervous System: Structure, Function and Disease Mechanisms.

Funding Information:
This work is funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant agreement no. 788363; “HITSCIL”) and Marie Sklodowska-Curie Actions Postdoctoral Fellowship of the European Commission (Project no. 898006; ‘MingleIFT’, A.M.)

Publisher Copyright:
© 2022 by the authors.

Funding

This work is funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant agreement no. 788363; “HITSCIL”) and Marie Sklodowska-Curie Actions Postdoctoral Fellowship of the European Commission (Project no. 898006; ‘MingleIFT’, A.M.)

Funders	Funder number
European Commission
European Research Council
HORIZON EUROPE Marie Sklodowska-Curie Actions
Horizon 2020 Framework Programme	788363, 898006

Keywords

axoneme
cilia
dynein
intraflagellar transport
kinesin
kinesin-2
microtubules
motor proteins
motor regulation

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10.3390/cells11172737

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Cite this

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title = "Mechanisms of Regulation in Intraflagellar Transport",

abstract = "Cilia are eukaryotic organelles essential for movement, signaling or sensing. Primary cilia act as antennae to sense a cell{\textquoteright}s environment and are involved in a wide range of signaling pathways essential for development. Motile cilia drive cell locomotion or liquid flow around the cell. Proper functioning of both types of cilia requires a highly orchestrated bi-directional transport system, intraflagellar transport (IFT), which is driven by motor proteins, kinesin-2 and IFT dynein. In this review, we explore how IFT is regulated in cilia, focusing from three different perspectives on the issue. First, we reflect on how the motor track, the microtubule-based axoneme, affects IFT. Second, we focus on the motor proteins, considering the role motor action, cooperation and motor-train interaction plays in the regulation of IFT. Third, we discuss the role of kinases in the regulation of the motor proteins. Our goal is to provide mechanistic insights in IFT regulation in cilia and to suggest directions of future research.",

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author = "Wouter Mul and Aniruddha Mitra and Peterman, \{Erwin J.G.\}",

note = "Special Issue: Primary Cilia in the Nervous System: Structure, Function and Disease Mechanisms. Funding Information: This work is funded by the European Research Council under the European Union{\textquoteright}s Horizon 2020 research and innovation program (Grant agreement no. 788363; “HITSCIL”) and Marie Sklodowska-Curie Actions Postdoctoral Fellowship of the European Commission (Project no. 898006; {\textquoteleft}MingleIFT{\textquoteright}, A.M.) Publisher Copyright: {\textcopyright} 2022 by the authors.",

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N2 - Cilia are eukaryotic organelles essential for movement, signaling or sensing. Primary cilia act as antennae to sense a cell’s environment and are involved in a wide range of signaling pathways essential for development. Motile cilia drive cell locomotion or liquid flow around the cell. Proper functioning of both types of cilia requires a highly orchestrated bi-directional transport system, intraflagellar transport (IFT), which is driven by motor proteins, kinesin-2 and IFT dynein. In this review, we explore how IFT is regulated in cilia, focusing from three different perspectives on the issue. First, we reflect on how the motor track, the microtubule-based axoneme, affects IFT. Second, we focus on the motor proteins, considering the role motor action, cooperation and motor-train interaction plays in the regulation of IFT. Third, we discuss the role of kinases in the regulation of the motor proteins. Our goal is to provide mechanistic insights in IFT regulation in cilia and to suggest directions of future research.

AB - Cilia are eukaryotic organelles essential for movement, signaling or sensing. Primary cilia act as antennae to sense a cell’s environment and are involved in a wide range of signaling pathways essential for development. Motile cilia drive cell locomotion or liquid flow around the cell. Proper functioning of both types of cilia requires a highly orchestrated bi-directional transport system, intraflagellar transport (IFT), which is driven by motor proteins, kinesin-2 and IFT dynein. In this review, we explore how IFT is regulated in cilia, focusing from three different perspectives on the issue. First, we reflect on how the motor track, the microtubule-based axoneme, affects IFT. Second, we focus on the motor proteins, considering the role motor action, cooperation and motor-train interaction plays in the regulation of IFT. Third, we discuss the role of kinases in the regulation of the motor proteins. Our goal is to provide mechanistic insights in IFT regulation in cilia and to suggest directions of future research.

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KW - microtubules

KW - motor proteins

KW - motor regulation

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ER -

Mechanisms of Regulation in Intraflagellar Transport

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Keywords

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