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PMID: 18784752 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein.

The EMBO journal ·Vol. 27 ·No. 19 ·2008-10-08 ·Pages 2471-83

Yamada M, Toba S, Yoshida Y, Haratani K, Mori D, Yano Y, Mimori-Kiyosue Y, Nakamura T, Itoh K, Fushiki S, Setou M, Wynshaw-Boris A, Torisawa T, Toyoshima YY, Hirotsune S

Abstract

LIS1 was first identified as a gene mutated in human classical lissencephaly sequence. LIS1 is required for dynein activity, but the underlying mechanism is poorly understood. Here, we demonstrate that LIS1 suppresses the motility of cytoplasmic dynein on microtubules (MTs), whereas NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. We demonstrate that LIS1, cytoplasmic dynein and MT fragments co-migrate anterogradely. When LIS1 function was suppressed by a blocking antibody, anterograde movement of cytoplasmic dynein was severely impaired. Immunoprecipitation assay indicated that cytoplasmic dynein forms a complex with LIS1, tubulins and kinesin-1. In contrast, immunoabsorption of LIS1 resulted in disappearance of co-precipitated tubulins and kinesin. Thus, we propose a novel model of the regulation of cytoplasmic dynein by LIS1, in which LIS1 mediates anterograde transport of cytoplasmic dynein to the plus end of cytoskeletal MTs as a dynein-LIS1 complex on transportable MTs, which is a possibility supported by our data.

MeSH Terms
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics,metabolism Animals Biological Transport/physiology Carrier Proteins/genetics,metabolism Cell Line Cytoplasm/metabolism Dyneins/genetics,metabolism Fluorescence Recovery After Photobleaching Humans Kinesins Microtubule-Associated Proteins/genetics,metabolism Microtubules/metabolism Neurons/cytology,physiology Recombinant Fusion Proteins/genetics,metabolism Swine Tubulin/genetics,metabolism
Chemicals
Carrier Proteins Microtubule-Associated Proteins NDEL1 protein, human Recombinant Fusion Proteins TUBB3 protein, human Tubulin 1-Alkyl-2-acetylglycerophosphocholine Esterase PAFAH1B1 protein, human Dyneins Kinesins
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Yamada Masami
Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Osaka, Japan.
Toba Shiori
Yoshida Yuko
Haratani Koji
Mori Daisuke
Yano Yoshihisa
Mimori-Kiyosue Yuko
Nakamura Takeshi
Itoh Kyoko
Fushiki Shinji
Setou Mitsutoshi
Wynshaw-Boris Anthony
Torisawa Takayuki
Toyoshima Yoko Y
Hirotsune Shinji
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2008.182
Published
2008-10-08
Epub
2008-00-11
Pages
2471-83
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2567412
Subset
IM
Grants
NICHD NIH HHS · R01 HD047380 · United States
NINDS NIH HHS · R01 NS041030 · United States
NINDS NIH HHS · NS41030 · United States
NICHD NIH HHS · HD47380 · United States
External Links
PubMed source DOI: 10.1038/emboj.2008.182 PMC Full Text View journal details
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