Shulin packages axonemal outer dynein arms for ciliary targeting

Girish R. Mali; Ferdos Abid Ali; Clinton K. Lau; Farida Begum; Jérôme Boulanger; Jonathan D. Howe; Zhuo A. Chen; Juri Rappsilber; Mark Skehel; Andrew P. Carter

doi:10.1126/science.abe0526

Shulin packages axonemal outer dynein arms for ciliary targeting

Girish R. Mali, Ferdos Abid Ali, Clinton K. Lau, Farida Begum, Jérôme Boulanger, Jonathan D. Howe, Zhuo A. Chen, Juri Rappsilber, Mark Skehel, Andrew P. Carter^*

^*Corresponding author for this work

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate Tetrahymena to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.

Original language	English
Article number	abe0526
Pages (from-to)	910-916
Number of pages	7
Journal	Science
Volume	371
Issue number	6532
DOIs	https://doi.org/10.1126/science.abe0526
Publication status	Published - 26 Feb 2021

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10.1126/science.abe0526

`Core Funding for the Wellcome Trust Centre for Cell Biology¿, Research Enrichment, Public Engagement
Tollervey, D. (Principal Investigator)
UK-based charities
1/12/18 → 1/06/22
Project: Research
Wellcome Centre for Cell Biology
Tollervey, D. (Principal Investigator)
UK-based charities
1/12/16 → 1/12/21
Project: Research
Proteomics at the Wellcome Trust Centre for Cell Biology (WTCCB) and School of Biological Sciences (SBS), Edinburgh
Rappsilber, J. (Principal Investigator)
UK-based charities
1/10/15 → 30/09/20
Project: Research

Cite this

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title = "Shulin packages axonemal outer dynein arms for ciliary targeting",

abstract = "The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate Tetrahymena to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.",

author = "Mali, {Girish R.} and Ali, {Ferdos Abid} and Lau, {Clinton K.} and Farida Begum and J{\'e}r{\^o}me Boulanger and Howe, {Jonathan D.} and Chen, {Zhuo A.} and Juri Rappsilber and Mark Skehel and Carter, {Andrew P.}",

year = "2021",

month = feb,

day = "26",

doi = "10.1126/science.abe0526",

language = "English",

volume = "371",

pages = "910--916",

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TY - JOUR

T1 - Shulin packages axonemal outer dynein arms for ciliary targeting

AU - Mali, Girish R.

AU - Ali, Ferdos Abid

AU - Lau, Clinton K.

AU - Begum, Farida

AU - Boulanger, Jérôme

AU - Howe, Jonathan D.

AU - Chen, Zhuo A.

AU - Rappsilber, Juri

AU - Skehel, Mark

AU - Carter, Andrew P.

PY - 2021/2/26

Y1 - 2021/2/26

N2 - The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate Tetrahymena to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.

AB - The main force generators in eukaryotic cilia and flagella are axonemal outer dynein arms (ODAs). During ciliogenesis, these ~1.8-megadalton complexes are assembled in the cytoplasm and targeted to cilia by an unknown mechanism. Here, we used the ciliate Tetrahymena to identify two factors (Q22YU3 and Q22MS1) that bind ODAs in the cytoplasm and are required for ODA delivery to cilia. Q22YU3, which we named Shulin, locked the ODA motor domains into a closed conformation and inhibited motor activity. Cryo-electron microscopy revealed how Shulin stabilized this compact form of ODAs by binding to the dynein tails. Our findings provide a molecular explanation for how newly assembled dyneins are packaged for delivery to the cilia.

U2 - 10.1126/science.abe0526

DO - 10.1126/science.abe0526

M3 - Article

C2 - 33632841

AN - SCOPUS:85101938371

SN - 0036-8075

VL - 371

SP - 910

EP - 916

JO - Science

JF - Science

IS - 6532

M1 - abe0526

ER -

Shulin packages axonemal outer dynein arms for ciliary targeting

Abstract

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Projects

`Core Funding for the Wellcome Trust Centre for Cell Biology¿, Research Enrichment, Public Engagement

Wellcome Centre for Cell Biology

Proteomics at the Wellcome Trust Centre for Cell Biology (WTCCB) and School of Biological Sciences (SBS), Edinburgh

Cite this