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The Centralspindlin proteins Pavarotti and Tumbleweed work with WASH to regulate Nuclear Envelope budding

View ORCID ProfileKerri A. Davidson, View ORCID ProfileMitsutoshi Nakamura, View ORCID ProfileJeffrey M. Verboon, View ORCID ProfileSusan M. Parkhurst
doi: https://doi.org/10.1101/2022.11.16.516846
Kerri A. Davidson
1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA 98109
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Mitsutoshi Nakamura
1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA 98109
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Jeffrey M. Verboon
1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA 98109
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Susan M. Parkhurst
1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA 98109
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  • For correspondence: susanp@fredhutch.org
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ABSTRACT

Nuclear envelope (NE) budding is a nuclear pore independent nuclear export pathway, analogous to the egress of herpesviruses, and required for protein quality control, synapse development and mitochondrial integrity. The physical formation of NE buds is dependent on the Wiskott-Aldrich Syndrome protein Wash, its regulatory complex (SHRC), and Arp2/3, and requires Wash’s actin nucleation activity. However, the machinery governing cargo recruitment and organization within the NE bud remains unknown. Here, we identify Pavarotti (Pav) and Tumbleweed (Tum) as new molecular components of NE budding. Pav and Tum interact directly with Wash and define a second nuclear Wash-containing complex required for NE budding. Interestingly, we find that the actin bundling activities of Wash and Pav are required, suggesting a structural role in the physical and/or organizational aspects of NE buds. Thus, Pav and Tum are providing exciting new entry points into the physical machineries of this alternative nuclear export pathway for large cargos during cell differentiation and development.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 17, 2022.
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The Centralspindlin proteins Pavarotti and Tumbleweed work with WASH to regulate Nuclear Envelope budding
Kerri A. Davidson, Mitsutoshi Nakamura, Jeffrey M. Verboon, Susan M. Parkhurst
bioRxiv 2022.11.16.516846; doi: https://doi.org/10.1101/2022.11.16.516846
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The Centralspindlin proteins Pavarotti and Tumbleweed work with WASH to regulate Nuclear Envelope budding
Kerri A. Davidson, Mitsutoshi Nakamura, Jeffrey M. Verboon, Susan M. Parkhurst
bioRxiv 2022.11.16.516846; doi: https://doi.org/10.1101/2022.11.16.516846

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