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

School of Biochemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

35 Citations (Scopus)

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
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

Bibliographical note

Keywords

Axonemal Dyneins/chemistry
Cilia/metabolism
Cryoelectron Microscopy
Cytoplasm/metabolism
Gene Knockdown Techniques
Image Processing, Computer-Assisted
Microtubules/physiology
Models, Molecular
Movement
Protein Binding
Protein Conformation
Protein Domains
Protozoan Proteins/chemistry
Tetrahymena thermophila/genetics

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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 \textasciitilde{}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.",

keywords = "Axonemal Dyneins/chemistry, Cilia/metabolism, Cryoelectron Microscopy, Cytoplasm/metabolism, Gene Knockdown Techniques, Image Processing, Computer-Assisted, Microtubules/physiology, Models, Molecular, Movement, Protein Binding, Protein Conformation, Protein Domains, Protozoan Proteins/chemistry, Tetrahymena thermophila/genetics",

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\}",

note = "Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2021",

month = feb,

day = "26",

doi = "10.1126/science.abe0526",

language = "English",

volume = "371",

pages = "910--916",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6532",

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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.

KW - Axonemal Dyneins/chemistry

KW - Cilia/metabolism

KW - Cryoelectron Microscopy

KW - Cytoplasm/metabolism

KW - Gene Knockdown Techniques

KW - Image Processing, Computer-Assisted

KW - Microtubules/physiology

KW - Models, Molecular

KW - Movement

KW - Protein Binding

KW - Protein Conformation

KW - Protein Domains

KW - Protozoan Proteins/chemistry

KW - Tetrahymena thermophila/genetics

U2 - 10.1126/science.abe0526

DO - 10.1126/science.abe0526

M3 - Article (Academic Journal)

C2 - 33632841

SN - 0036-8075

VL - 371

SP - 910

EP - 916

JO - Science

JF - Science

IS - 6532

ER -

Shulin packages axonemal outer dynein arms for ciliary targeting

Abstract

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