Beyond microtubules: The cellular environment at the endoplasmic reticulum attracts proteins to the nucleus, enabling nuclear transport

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. [Display omitted] •The interaction of proteins with ER slows down their diffusion at the perinucleus•This leads proteins to migrate toward the perinucleus without ATP consumption•Frequent ER interaction of larger proteins promotes perinuclear accumulation•Diffusion with the physical interaction can be described by Chapman’s law Cell biology; Biophysics; Computer simulation