Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state
| Autor: | Zhanna Hakhverdyan, David J Thaller, Sapan Borah, Megan C. King, Elisa C. Rodriguez, Anthony W Isenhour, C. Patrick Lusk, Michael P. Rout |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Saccharomyces cerevisiae Proteins Membrane Proteins Nuclear Proteins food and beverages Saccharomyces cerevisiae Articles Cell Biology Computational biology Biology Nuclear Pore Complex Proteins stomatognathic diseases 03 medical and health sciences 0302 clinical medicine Schizosaccharomyces Nuclear Pore otorhinolaryngologic diseases Schizosaccharomyces pombe Proteins NPC assembly Molecular Biology 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e20-09-0584 |
| Popis: | Integral membrane proteins of the Lap2-emerin-MAN1 (LEM) family have emerged as important components of the inner nuclear membrane (INM) required for the functional and physical integrity of the nuclear envelope. However, like many INM proteins, there is limited understanding of the biochemical interaction networks that enable LEM protein function. Here, we show that Heh2/Man1 can interact with major scaffold components of the nuclear pore complex (NPC), specifically the inner ring complex (IRC), in evolutionarily distant yeasts. Although an N-terminal domain is required for Heh2 targeting to the INM, we demonstrate that more stable interactions with the NPC are mediated by a C-terminal winged helix (WH) domain, thus decoupling INM targeting and NPC binding. Inhibiting Heh2’s interactions with the NPC by deletion of the Heh2 WH domain leads to NPC clustering. Interestingly, Heh2’s association with NPCs can also be disrupted by knocking out several outer ring nucleoporins. Thus, Heh2’s interaction with NPCs depends on the structural integrity of both major NPC scaffold complexes. We propose a model in which Heh2 acts as a sensor of NPC assembly state, which may be important for NPC quality control mechanisms and the segregation of NPCs during cell division. |
| Databáze: | OpenAIRE |
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