MARK4 enhances stress granule formation and increases tau accumulation

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 Alzheimer’s 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.