RNA Granules Hitchhike on Lysosomes for Long-Distance Transport, Using Annexin A11 as a Molecular Tether

Complex neural circuitry requires stable connections formed by lengthy axons. To maintain these functional circuits, fast transport delivers RNAs to distal axons where they undergo local translation. However, the mechanism that enables long-distance transport of RNA granules is not yet understood. Here, we demonstrate that a complex containing RNA and the RNA-binding protein (RBP) SFPQ interacts selectively with a tetrameric kinesin containing the adaptor KLC1 and the motor KIF5A. We show that the binding of SFPQ to the KIF5A/KLC1 motor complex is required for axon survival and is impacted by KIF5A mutations that cause Charcot-Marie Tooth (CMT) disease. Moreover, therapeutic approaches that bypass the need for local translation of SFPQ-bound proteins prevent axon degeneration in CMT models. Collectively, these observations indicate that KIF5A-mediated SFPQ-RNA granule transport may be a key function disrupted in KIF5A-linked neurologic diseases and that replacing axonally translated proteins serves as a therapeutic approach to axonal degenerative disorders.

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Fast Transport of RNA Granules by Direct Interactions with KIF5A/KLC1 Motors Prevents Axon Degeneration

10.1101/2020.02.02.931204 ◽

2020 ◽

Cited By ~ 3

Author(s):

Yusuke Fukuda ◽

Maria F. Pazyra-Murphy ◽

Ozge E. Tasdemir-Yilmaz ◽

Yihang Li ◽

Lillian Rose ◽

...

Keyword(s):

Rna Binding ◽

Axon Degeneration ◽

Local Translation ◽

Long Distance ◽

Rna Granules ◽

Long Distance Transport ◽

Degenerative Disorders ◽

Fast Transport ◽

Axon Survival ◽

Distance Transport

AbstractComplex neural circuitry requires stable connections formed by lengthy axons. To maintain these functional circuits, fast transport delivers RNAs to distal axons where they undergo local translation. However, the mechanism that enables long distance transport of non-membrane enclosed organelles such as RNA granules is not known. Here we demonstrate that a complex containing RNA and the RNA-binding protein (RBP) SFPQ interacts directly with a tetrameric kinesin containing the adaptor KLC1 and the motor KIF5A. We show that binding of SFPQ to KIF5A/KLC1 motor complex is required for axon survival and is impacted by KIF5A mutations that cause Charcot-Marie-Tooth (CMT) Disease. Moreover, therapeutic approaches that bypass the need for local translation of SFPQ-bound proteins prevent axon degeneration in CMT models. Collectively, these observations show that non-membrane enclosed organelles can move autonomously and that replacing axonally translated proteins provides a therapeutic approach to axonal degenerative disorders.

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The Fine Structure of Phloem Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119867 ◽

1985 ◽

Vol 43 ◽

pp. 632-635

Author(s):

James Cronshaw

Keyword(s):

Structural Studies ◽

High Concentration ◽

Long Distance ◽

Phloem Tissue ◽

Sieve Elements ◽

Long Distance Transport ◽

P Protein ◽

Companion Cells ◽

Electron Microscopical ◽

Distance Transport

Long distance transport in plants takes place in phloem tissue which has characteristic cells, the sieve elements. At maturity these cells have sieve areas in their end walls with specialized perforations. They are associated with companion cells, parenchyma cells, and in some species, with transfer cells. The protoplast of the functioning sieve element contains a high concentration of sugar, and consequently a high hydrostatic pressure, which makes it extremely difficult to fix mature sieve elements for electron microscopical observation without the formation of surge artifacts. Despite many structural studies which have attempted to prevent surge artifacts, several features of mature sieve elements, such as the distribution of P-protein and the nature of the contents of the sieve area pores, remain controversial.

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