Version 1
: Received: 29 July 2024 / Approved: 30 July 2024 / Online: 30 July 2024 (13:38:00 CEST)
How to cite:
Fritze, J. S.; Stiehler, F. F.; Wolfrum, U. Nuclear-Cytoplasmic Shuttling of the Usher Syndrome 1G Protein SANS Differs from Its Paralogue ANKS4B. Preprints2024, 2024072436. https://doi.org/10.20944/preprints202407.2436.v1
Fritze, J. S.; Stiehler, F. F.; Wolfrum, U. Nuclear-Cytoplasmic Shuttling of the Usher Syndrome 1G Protein SANS Differs from Its Paralogue ANKS4B. Preprints 2024, 2024072436. https://doi.org/10.20944/preprints202407.2436.v1
Fritze, J. S.; Stiehler, F. F.; Wolfrum, U. Nuclear-Cytoplasmic Shuttling of the Usher Syndrome 1G Protein SANS Differs from Its Paralogue ANKS4B. Preprints2024, 2024072436. https://doi.org/10.20944/preprints202407.2436.v1
APA Style
Fritze, J. S., Stiehler, F. F., & Wolfrum, U. (2024). Nuclear-Cytoplasmic Shuttling of the Usher Syndrome 1G Protein SANS Differs from Its Paralogue ANKS4B. Preprints. https://doi.org/10.20944/preprints202407.2436.v1
Chicago/Turabian Style
Fritze, J. S., Felizitas F. Stiehler and Uwe Wolfrum. 2024 "Nuclear-Cytoplasmic Shuttling of the Usher Syndrome 1G Protein SANS Differs from Its Paralogue ANKS4B" Preprints. https://doi.org/10.20944/preprints202407.2436.v1
Abstract
The USH1G protein SANS is a small multifunctional scaffold protein. It is involved in several different cellular processes, such as intracellular transport, in the cytoplasm, or splicing of pre-mRNA, in the cell nucleus. Here, we aimed to gain insight into the regulation of the subcellular localization and the nuclear-cytoplasmic shuttling of SANS and its paralogue ANKS4B, not yet reported in the nucleus. We identified karyopherins mediating the nuclear import and export by screening the nuclear interactome of SANS. Sequence analyses predicted in silico evolutionarily conserved nuclear localization sequences (NLSs) and nuclear export sequences (NESs) in SANS, but only NESs in ANKS4B, which are suitable for karyopherin binding.Quantifying the nuclear-cytoplasmic localization of wild-type SANS and NLS/NES mutants, we experimentally confirmed in silico predicted NLS and NES functioning in the nuclear-cytoplasmic shuttling in situ in cells. The comparison of SANS and its paralogue ANKS4B revealed substantial differences in the interaction with the nuclear splicing protein PRPF31 and in their nuclear localization. Finally, our results on pathogenic USH1G/SANS mutants suggest that the loss of NLSs and NESs and thereby the ability to control nuclear-cytoplasmic shuttling is disease-relevant.
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
