Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility

Danielle A. Grotjahn, Saikat Chowdhury, Yiru Xu, Richard Mckenney, Trina A. Schroer, Gabriel C. Lander

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cytoplasmic dynein is a protein complex that transports molecular cargo along microtubules (MTs), playing a key role in the intracellular trafficking network. Vertebrate dynein's movement becomes strikingly enhanced upon interacting with dynactin and a cargo adaptor such as BicaudalD2. However, the mechanisms responsible for increased transport activity are not well understood, largely owing to limited structural information. We used cryo-electron tomography (cryo-ET) to visualize the 3D structure of the MT-bound dynein-dynactin complex from Mus musculus and show that the dynactin-cargo adaptor complex binds two dimeric dyneins. This configuration imposes spatial and conformational constraints on both dynein dimers, positioning the four motor domains in proximity to one another and oriented toward the MT minus end. We propose that grouping multiple dyneins onto a single dynactin scaffold promotes collective force production, increased processivity, and unidirectional movement, suggesting mechanistic parallels to axonemal dynein. These findings provide structural insights into a previously unknown mechanism for dynein regulation.

Original languageEnglish (US)
Pages (from-to)203-207
Number of pages5
JournalNature Structural and Molecular Biology
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Electron Microscope Tomography
Dyneins
Microtubules
Axonemal Dyneins
Cytoplasmic Dyneins
Protein Transport
Vertebrates
Dynactin Complex

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility. / Grotjahn, Danielle A.; Chowdhury, Saikat; Xu, Yiru; Mckenney, Richard; Schroer, Trina A.; Lander, Gabriel C.

In: Nature Structural and Molecular Biology, Vol. 25, No. 3, 01.03.2018, p. 203-207.

Research output: Contribution to journalArticle

Grotjahn, Danielle A. ; Chowdhury, Saikat ; Xu, Yiru ; Mckenney, Richard ; Schroer, Trina A. ; Lander, Gabriel C. / Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility. In: Nature Structural and Molecular Biology. 2018 ; Vol. 25, No. 3. pp. 203-207.
@article{6efce9ccf4a845f1963e239b0bdd5b32,
title = "Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility",
abstract = "Cytoplasmic dynein is a protein complex that transports molecular cargo along microtubules (MTs), playing a key role in the intracellular trafficking network. Vertebrate dynein's movement becomes strikingly enhanced upon interacting with dynactin and a cargo adaptor such as BicaudalD2. However, the mechanisms responsible for increased transport activity are not well understood, largely owing to limited structural information. We used cryo-electron tomography (cryo-ET) to visualize the 3D structure of the MT-bound dynein-dynactin complex from Mus musculus and show that the dynactin-cargo adaptor complex binds two dimeric dyneins. This configuration imposes spatial and conformational constraints on both dynein dimers, positioning the four motor domains in proximity to one another and oriented toward the MT minus end. We propose that grouping multiple dyneins onto a single dynactin scaffold promotes collective force production, increased processivity, and unidirectional movement, suggesting mechanistic parallels to axonemal dynein. These findings provide structural insights into a previously unknown mechanism for dynein regulation.",
author = "Grotjahn, {Danielle A.} and Saikat Chowdhury and Yiru Xu and Richard Mckenney and Schroer, {Trina A.} and Lander, {Gabriel C.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1038/s41594-018-0027-7",
language = "English (US)",
volume = "25",
pages = "203--207",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Cryo-electron tomography reveals that dynactin recruits a team of dyneins for processive motility

AU - Grotjahn, Danielle A.

AU - Chowdhury, Saikat

AU - Xu, Yiru

AU - Mckenney, Richard

AU - Schroer, Trina A.

AU - Lander, Gabriel C.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Cytoplasmic dynein is a protein complex that transports molecular cargo along microtubules (MTs), playing a key role in the intracellular trafficking network. Vertebrate dynein's movement becomes strikingly enhanced upon interacting with dynactin and a cargo adaptor such as BicaudalD2. However, the mechanisms responsible for increased transport activity are not well understood, largely owing to limited structural information. We used cryo-electron tomography (cryo-ET) to visualize the 3D structure of the MT-bound dynein-dynactin complex from Mus musculus and show that the dynactin-cargo adaptor complex binds two dimeric dyneins. This configuration imposes spatial and conformational constraints on both dynein dimers, positioning the four motor domains in proximity to one another and oriented toward the MT minus end. We propose that grouping multiple dyneins onto a single dynactin scaffold promotes collective force production, increased processivity, and unidirectional movement, suggesting mechanistic parallels to axonemal dynein. These findings provide structural insights into a previously unknown mechanism for dynein regulation.

AB - Cytoplasmic dynein is a protein complex that transports molecular cargo along microtubules (MTs), playing a key role in the intracellular trafficking network. Vertebrate dynein's movement becomes strikingly enhanced upon interacting with dynactin and a cargo adaptor such as BicaudalD2. However, the mechanisms responsible for increased transport activity are not well understood, largely owing to limited structural information. We used cryo-electron tomography (cryo-ET) to visualize the 3D structure of the MT-bound dynein-dynactin complex from Mus musculus and show that the dynactin-cargo adaptor complex binds two dimeric dyneins. This configuration imposes spatial and conformational constraints on both dynein dimers, positioning the four motor domains in proximity to one another and oriented toward the MT minus end. We propose that grouping multiple dyneins onto a single dynactin scaffold promotes collective force production, increased processivity, and unidirectional movement, suggesting mechanistic parallels to axonemal dynein. These findings provide structural insights into a previously unknown mechanism for dynein regulation.

UR - http://www.scopus.com/inward/record.url?scp=85041730919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041730919&partnerID=8YFLogxK

U2 - 10.1038/s41594-018-0027-7

DO - 10.1038/s41594-018-0027-7

M3 - Article

C2 - 29416113

AN - SCOPUS:85041730919

VL - 25

SP - 203

EP - 207

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 3

ER -