eprintid: 36170
rev_number: 21
eprint_status: archive
userid: 8833
dir: disk0/00/03/61/70
datestamp: 2025-03-10 08:56:10
lastmod: 2025-03-10 08:56:26
status_changed: 2025-03-10 08:56:10
type: doctoralThesis
metadata_visibility: show
creators_name: Mikus, Felix
title: Compositional heterogeneity and homeostasis of the nuclear pore complex
subjects: ddc-500
subjects: ddc-570
divisions: i-140001
divisions: i-850800
adv_faculty: af-14
cterms_swd: Cytologie
cterms_swd: Hefeartige Pilze
cterms_swd: Zellkern
abstract: Nuclear pore complexes (NPCs) are essential and deeply conserved structure in eukaryotes and act as gateways between the cytoplasm and the nucleoplasm. The major purpose of NPCs is transport of proteins and RNA across the nuclear envelope (NE). They are further involved as key players in a plethora of critical functions such transcriptional regulation, mRNA maturation, and regulation of cell division. Which of those functions pores are participating in relies on both their molecular compositions and their location. While the structure of NPCs has been closely investigated and largely solved across several species using a multitude of techniques, temporal and spatial dynamics still remain poorly understood.
In this thesis, I demonstrate that different strategies exist across eukaryotes to distribute NPCs across the NE. Pore densities were surveyed across three yeasts, two ciliates, and a single diatom species using expansion microscopy. This represents the first study comparing densities across a variety of species using the same method, which could be easily adapted by the field going forward.
I further investigate mechanisms by which a subpopulation of pores, missing their most distal basket nucleoporins (TPR proteins), regulates nuclear envelope breakdown (NEBD) in the fission yeast Schizosaccharomyces pombe. The presence of TPR homologues within the mitotic midzone interferes with NPC disassembly, thereby delaying NEBD.
Additionally, extranuclear accumulations of NPCs were observed upon disrupting NPC homeostasis. Data indicates diameters of NPCs residing within those structures to be reduced significantly despite being maintained for several cell cycles. These results highlight how the diverse roles played by NPCs across species and functional contexts depend on specialised subpopulations with unique composition and spatial distributions, setting the stage for future investigations of this fundamental regulator of the interface between nucleoplasm and cytoplasm.
date: 2026
id_scheme: DOI
id_number: 10.11588/heidok.00036170
own_urn: urn:nbn:de:bsz:16-heidok-361704
date_accepted: 2025-02-03
advisor: HASH(0x55e83b5bf7b8)
language: eng
bibsort: MIKUSFELIXCOMPOSITIO
full_text_status: restricted
place_of_pub: Heidelberg
citation:   Mikus, Felix  (2026) Compositional heterogeneity and homeostasis of the nuclear pore complex.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/36170/1/20241118_Thesis_FelixMikus.pdf