An amphipathic helix in Brl1 is required for nuclear pore complex biogenesis in S. cerevisiae

Annemarie Kralt, Matthias Wojtynek, Jonas S. Fischer, Arantxa Agote-Aran, Roberta Mancini, Elisa Dultz, Elad Noor, Federico Uliana, Marianna Tatarek-Nossol, Wolfram Antonin, Evgeny Onischenko, Ohad Medalia, Karsten Weis

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The nuclear pore complex (NPC) is the central portal for macromolecular exchange between the nucleus and cytoplasm. In all eukaryotes, NPCs assemble into an intact nuclear envelope (NE) during interphase, but the process of NPC biogenesis remains poorly characterized. Furthermore, little is known about how NPC assembly leads to the fusion of the outer and inner NE, and no factors have been identified that could trigger this event. Here, we characterize the trans-membrane protein Brl1 as an NPC assembly factor required for NE fusion in budding yeast. Brl1 preferentially associates with NPC assembly intermediates and its depletion halts NPC biogenesis, leading to NE herniations that contain inner and outer ring nucleoporins but lack the cytoplasmic export platform. Furthermore, we identify an essential amphipathic helix in the luminal domain of Brl1 that mediates interactions with lipid bilayers. Mutations in this amphipathic helix lead to NPC assembly defects, and cryo-electron tomography analyses reveal multilayered herniations of the inner nuclear membrane with NPC-like structures at the neck, indicating a failure in NE fusion. Taken together, our results identify a role for Brl1 in NPC assembly and suggest a function of its amphipa-thic helix in mediating the fusion of the inner and outer nuclear membranes.

Original languageEnglish
Article numbere78385
JournaleLife
Volume11
DOIs
StatePublished - 1 Jan 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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