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Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation
Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226478/ https://www.ncbi.nlm.nih.gov/pubmed/21976701 http://dx.doi.org/10.1091/mbc.E11-01-0068 |
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author | Matsuzaki, Fumiko Shirane, Michiko Matsumoto, Masaki Nakayama, Keiichi I. |
author_facet | Matsuzaki, Fumiko Shirane, Michiko Matsumoto, Masaki Nakayama, Keiichi I. |
author_sort | Matsuzaki, Fumiko |
collection | PubMed |
description | Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and -B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin–KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin–KIF5 axis appears to be integral to neuronal function. |
format | Online Article Text |
id | pubmed-3226478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-32264782012-02-16 Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation Matsuzaki, Fumiko Shirane, Michiko Matsumoto, Masaki Nakayama, Keiichi I. Mol Biol Cell Articles Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and -B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin–KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin–KIF5 axis appears to be integral to neuronal function. The American Society for Cell Biology 2011-12-01 /pmc/articles/PMC3226478/ /pubmed/21976701 http://dx.doi.org/10.1091/mbc.E11-01-0068 Text en © 2011 Matsuzaki 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 Biology. |
spellingShingle | Articles Matsuzaki, Fumiko Shirane, Michiko Matsumoto, Masaki Nakayama, Keiichi I. Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation |
title | Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation |
title_full | Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation |
title_fullStr | Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation |
title_full_unstemmed | Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation |
title_short | Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation |
title_sort | protrudin serves as an adaptor molecule that connects kif5 and its cargoes in vesicular transport during process formation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226478/ https://www.ncbi.nlm.nih.gov/pubmed/21976701 http://dx.doi.org/10.1091/mbc.E11-01-0068 |
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