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BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

Cytoplasmic dynein is the major microtubule minus-end–directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein–dynactin interaction are poorly understood. In this study, we focus on dynein–dynactin recruitment to cargo by the conserved mo...

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Autores principales: Splinter, Daniël, Razafsky, David S., Schlager, Max A., Serra-Marques, Andrea, Grigoriev, Ilya, Demmers, Jeroen, Keijzer, Nanda, Jiang, Kai, Poser, Ina, Hyman, Anthony A., Hoogenraad, Casper C., King, Stephen J., Akhmanova, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484101/
https://www.ncbi.nlm.nih.gov/pubmed/22956769
http://dx.doi.org/10.1091/mbc.E12-03-0210
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author Splinter, Daniël
Razafsky, David S.
Schlager, Max A.
Serra-Marques, Andrea
Grigoriev, Ilya
Demmers, Jeroen
Keijzer, Nanda
Jiang, Kai
Poser, Ina
Hyman, Anthony A.
Hoogenraad, Casper C.
King, Stephen J.
Akhmanova, Anna
author_facet Splinter, Daniël
Razafsky, David S.
Schlager, Max A.
Serra-Marques, Andrea
Grigoriev, Ilya
Demmers, Jeroen
Keijzer, Nanda
Jiang, Kai
Poser, Ina
Hyman, Anthony A.
Hoogenraad, Casper C.
King, Stephen J.
Akhmanova, Anna
author_sort Splinter, Daniël
collection PubMed
description Cytoplasmic dynein is the major microtubule minus-end–directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein–dynactin interaction are poorly understood. In this study, we focus on dynein–dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo. Direct visualization of dynein in live cells indicates that by itself the triple BICD2-N–dynein–dynactin complex is unable to interact with either cargo or microtubules. However, tethering of BICD2-N to different membranes promotes their microtubule minus-end–directed motility. We further show that LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and that LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors.
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spelling pubmed-34841012013-01-16 BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures Splinter, Daniël Razafsky, David S. Schlager, Max A. Serra-Marques, Andrea Grigoriev, Ilya Demmers, Jeroen Keijzer, Nanda Jiang, Kai Poser, Ina Hyman, Anthony A. Hoogenraad, Casper C. King, Stephen J. Akhmanova, Anna Mol Biol Cell Articles Cytoplasmic dynein is the major microtubule minus-end–directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein–dynactin interaction are poorly understood. In this study, we focus on dynein–dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo. Direct visualization of dynein in live cells indicates that by itself the triple BICD2-N–dynein–dynactin complex is unable to interact with either cargo or microtubules. However, tethering of BICD2-N to different membranes promotes their microtubule minus-end–directed motility. We further show that LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and that LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors. The American Society for Cell Biology 2012-11-01 /pmc/articles/PMC3484101/ /pubmed/22956769 http://dx.doi.org/10.1091/mbc.E12-03-0210 Text en © 2012 Splinter et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Splinter, Daniël
Razafsky, David S.
Schlager, Max A.
Serra-Marques, Andrea
Grigoriev, Ilya
Demmers, Jeroen
Keijzer, Nanda
Jiang, Kai
Poser, Ina
Hyman, Anthony A.
Hoogenraad, Casper C.
King, Stephen J.
Akhmanova, Anna
BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
title BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
title_full BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
title_fullStr BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
title_full_unstemmed BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
title_short BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
title_sort bicd2, dynactin, and lis1 cooperate in regulating dynein recruitment to cellular structures
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484101/
https://www.ncbi.nlm.nih.gov/pubmed/22956769
http://dx.doi.org/10.1091/mbc.E12-03-0210
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