Back

MARK4 enhances stress granule formation and increases tau accumulation

Nakajima, S.; Sultanakhmetov, G.; Fukuchi, A.; Watanabe, K.; Ito, K.; Shimizu, S.; Asada, A.; Saito, T.; Ando, K.

2025-05-02 cell biology
10.1101/2025.04.30.651577 bioRxiv
Show abstract

Stress granules (SGs) are membrane-less organelles that are formed in response to cellular stress. SGs protect cells against stress; however, their dysregulation and persistence may contribute to neurodegeneration. Microtubule-affinity regulating kinase 4 (MARK4) phosphorylates microtubule-binding protein tau and its abnormal activation has been linked to Alzheimers disease. Here, we report that MARK4 is a component of SGs and enhances SG formation. MARK4 colocalizes with T-cell intracellular antigen 1 (TIA1) in SGs, and MARK4 expression enhances the formation of SGs in cultured mammalian cells. MARK4 localization to SGs is mediated by its spacer domain, and MARK4 localization to SGs and its kinase activity is required for the enhancement of SG formation. We found that MARK4 and TIA1 synergistically caused the accumulation of tau proteins in cultured cells, and the knockdown of a fly homolog of TIA1 suppressed tau toxicity in a Drosophila model. These results indicate that MARK4 activity affects SG formation and suggest that MARK4 and TIA1 synergistically contribute to tau toxicity.

Matching journals

The top 6 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.