Distinct RanBP1 nuclear export and cargo dissociation mechanisms between fungi and animals

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Abstract

Ran binding protein 1 (RanBP1) is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport. Much of what we know about RanBP1 is learned from fungi. Intrigued by the long-standing paradox of harbouring an extra NES in animal RanBP1, we discovered utterly unexpected cargo dissociation and nuclear export mechanisms for animal RanBP1. In contrast to CRM1-RanGTP sequestration mechanism of cargo dissociation in fungi, animal RanBP1 solely sequestered RanGTP from nuclear export complexes. In fungi, RanBP1, CRM1 and RanGTP formed a 1:1:1 nuclear export complex; in contrast, animal RanBP1, CRM1 and RanGTP formed a 1:1:2 nuclear export complex. The key feature for the two mechanistic changes from fungi to animals was the loss of affinity between RanBP1-RanGTP and CRM1, since residues mediating their interaction in fungi were not conserved in animals. The biological significances of these different mechanisms in fungi and animals were also studied.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Yuling Li

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Jinhan Zhou

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Sui Min

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Yang Zhang

Division of Abdominal Cancer, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Yuqing Zhang

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Qiao Zhou

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Xiaofei Shen

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, Division of Neurology, West China Second University Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Da Jia

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, Division of Neurology, West China Second University Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Junhong Han

Division of Abdominal Cancer, State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, Sichuan University, Chengdu, China

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The authors declare that no competing interests exist.
Qingxiang Sun

Department of Pathology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China

For correspondence
sunqingxiang@hotmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9474-8882

Funding

National Natural Science Foundation of China (80502629)

Qingxiang Sun

National Natural Science Foundation of China (31671477)

Da Jia

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.