Modeling Protein Diffusion Across ER-Nuclear Envelope Junctions Reveals Efficient Transport via Simple Diffusion

Fuente: arXiv
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Main Authors: Merino-Aceituno, Sara, Moschella, Carmela, Otsuka, Shotaro, Schmeiser, Christian, Scholz, Julia
Format: Preprint
Published: 2025
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author Merino-Aceituno, Sara
Moschella, Carmela
Otsuka, Shotaro
Schmeiser, Christian
Scholz, Julia
author_facet Merino-Aceituno, Sara
Moschella, Carmela
Otsuka, Shotaro
Schmeiser, Christian
Scholz, Julia
contents The endoplasmic reticulum (ER) is the largest continuous membrane-bound organelle in the cell and plays a central role in the synthesis and turnover of many lipids and proteins. It connects directly to the nucleus through specialized contact points known as ER-nuclear envelope (NE) junctions. In our recent study, we found that these ER-NE junctions are both narrow and infrequent, measuring less than 20 nanometers in diameter and occurring at a frequency of approximately 0.1 per square micrometer. However, it remains unclear whether such limited and narrow connections are sufficient to support efficient transport between the ER and NE. Here, we built a mathematical model of ER-to-NE protein diffusion, incorporating ultrastructural parameters, the frequency of ER-NE junctions, and the diffusion coefficient of proteins within the ER lumen. To validate the model, we experimentally quantified the transport rate of ER luminal proteins to the NE using fluorescence recovery after photobleaching (FRAP). Our model and experimental data demonstrate that simple diffusion is sufficient to account for the rapid transport of proteins from the ER to the NE, despite the limited and narrow nature of the connecting junctions. Together, these findings offer mechanistic insight into how ER-NE connectivity enables rapid protein transport and lay the groundwork for future studies on ER-nucleus communication.
format Preprint
id arxiv_https___arxiv_org_abs_2510_09479
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Modeling Protein Diffusion Across ER-Nuclear Envelope Junctions Reveals Efficient Transport via Simple Diffusion
Merino-Aceituno, Sara
Moschella, Carmela
Otsuka, Shotaro
Schmeiser, Christian
Scholz, Julia
Mathematical Physics
The endoplasmic reticulum (ER) is the largest continuous membrane-bound organelle in the cell and plays a central role in the synthesis and turnover of many lipids and proteins. It connects directly to the nucleus through specialized contact points known as ER-nuclear envelope (NE) junctions. In our recent study, we found that these ER-NE junctions are both narrow and infrequent, measuring less than 20 nanometers in diameter and occurring at a frequency of approximately 0.1 per square micrometer. However, it remains unclear whether such limited and narrow connections are sufficient to support efficient transport between the ER and NE. Here, we built a mathematical model of ER-to-NE protein diffusion, incorporating ultrastructural parameters, the frequency of ER-NE junctions, and the diffusion coefficient of proteins within the ER lumen. To validate the model, we experimentally quantified the transport rate of ER luminal proteins to the NE using fluorescence recovery after photobleaching (FRAP). Our model and experimental data demonstrate that simple diffusion is sufficient to account for the rapid transport of proteins from the ER to the NE, despite the limited and narrow nature of the connecting junctions. Together, these findings offer mechanistic insight into how ER-NE connectivity enables rapid protein transport and lay the groundwork for future studies on ER-nucleus communication.
title Modeling Protein Diffusion Across ER-Nuclear Envelope Junctions Reveals Efficient Transport via Simple Diffusion
topic Mathematical Physics
url https://arxiv.org/abs/2510.09479