All proteins are translated in the cytoplasm, yet many, including transcription factors, play vital roles in the nucleus. While previous research has concentrated on molecular motors for the transport of these proteins to the nucleus, recent observations reveal perinuclear accumulation even in the absence of an energy source, hinting at alternative mechanisms. Here, we propose that structural properties of the cellular environment, specifically the endoplasmic reticulum (ER), can promote molecular transport to the perinucleus without requiring additional energy expenditure. Specifically, physical interaction between proteins and the ER impedes their diffusion and leads to their accumulation near the nucleus. This result explains why larger proteins, more frequently interacting with the ER membrane, tend to accumulate at the perinucleus. Interestingly, such diffusion in a heterogeneous environment follows Chapman’s law rather than the popular Fick’s law. Our findings suggest a novel protein transport mechanism arising solely from characteristics of the intracellular environment.
(In press for Nature Communications) scLENS : Data-driven signal detection for unbiased scRNA-seq data analysis
Hyun Kim+, Won Chang, Seok Joo Chae, and 3 more authors
2024
(In minor revision for PLoS Computational Biology) Beyond homogeneity: Assessing the validity of the Michaelis–Menten rate law in spatially heterogeneous Environments
Seolah Shin+, Seok Joo Chae+, Seunggyu Lee, and 1 more author
2024
(Under Review in Science Advances) NK killing activity is determined by activator-driven gating
Sunyoung Lee+, Seok Joo Chae+, In-Hwan Jang, and 8 more authors
2024
(In Preparatßion) Predicting the risk of PTSD among a nationwide cohort of firefighters using a machine learning algorithm
The circadian (∼24h) clock is based on a negative-feedback loop centered around the PERIOD protein (PER), translated in the cytoplasm and then enters the nucleus to repress its own transcription at the right time of day. Such precise nucleus entry is mysterious because thousands of PER molecules transit through crowded cytoplasm and arrive at the perinucleus across several hours. To understand this, we developed a mathematical model describing the complex spatiotemporal dynamics of PER as a single random time delay. We find that the spatially coordinated bistable phosphoswitch of PER, which triggers the phosphorylation of accumulated PER at the perinucleus, leads to the synchronous and precise nuclear entry of PER. This leads to robust circadian rhythms even when PER arrival times are heterogeneous and perturbed due to changes in cell crowdedness, cell size, and transcriptional activator levels. This shows how the circadian clock compensates for spatiotemporal noise.
2018
Uncovering Hierarchical Structure in Social Networks Using Isosxpectral Reductions
Leonid A. Bunimovich, Chi-Jen Wang, Seokjoo Chae, and 1 more author
In 2018 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining (ASONAM), 2018
Beyond microtubules: The cellular environment at the endoplasmic reticulum attracts proteins to the nucleus, enabling nuclear transportiScience, 2024
Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeepingiScience, 2023
Uncovering Hierarchical Structure in Social Networks Using Isosxpectral ReductionsIn 2018 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining (ASONAM), 2018