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Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation
Abstract
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.
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A tripartite complex between Rab7, FYCO1, and kinesin promotes outward lysosomal movement.
“a tripartite complex between Rab7, FYCO1, and kinesin has also been shown to promote outward lysosomal movement21,22.”
From TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes (2017) · cites this paper as [21]
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Rab GTPases as coordinators of vesicle traffic
Stenmark, H. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2728 · Cited by 3,413
Kinesin superfamily motor proteins and intracellular transport
Hirokawa, N., Noda, Y., Tanaka, Y., & Niwa, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2774 · Cited by 1,859 · cited 3×
“KIF5 is responsible for such proper distribution of a large number of cargo proteins associated with various types of intracellular vesicles (Hirokawa et al., 2009).”
InfluentialKinesin׳s tail domain is an inhibitory regulator of the motor domain
Coy, D. L., Hancock, W. O., Wagenbach, M., & Howard, J. (1999) · Nature Cell Biology · doi:10.1038/13001 · Cited by 329
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Self-citationTMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models
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Metadata
- Authors
- Matsuzaki, F., Shirane, M., Matsumoto, M., & Nakayama, K. I.
- Venue
- Molecular Biology of the Cell
- Published
- 2011-12
- Volume
- 22
- Issue
- 23
- Pages
- 4602-4620
- ISSN
- 1059-1524
- 1939-4586
- PMC
- PMC3226478
- Cited by
- 118
- References
- 3
- Language
- en
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