ULK1/2 Restricts the Formation of Inducible SINT-Speckles, Membraneless Organelles Controlling the Threshold of TBK1 Activation

Saul, Vera Vivian; Seibert, Markus; Krüger, Marcus; Jeratsch, Sylvia; Kracht, Michael; Schmitz, Michael Lienhard

The severe fever thrombocytopenia syndrome phlebovirus non-structural protein S (NSs) targets the ABIN2/p105 complex to activate proviral signaling cascades (Choi et al., 2019) . As ABIN2 is a core component of SINT-speckles it was interesting to investigate whether the NSs protein also can be recruited to these MLOs. Immunofluorescence analysis not only confirmed the described cytosolic localization of NSs (Choi et al., 2019) but also revealed a fraction of NSs in colocalization with ABIN2 ( Figure 8A ). Induction of cell stress by arsenite or heat shock resulted in an increased recruitment of NSs to SINT-speckles (Figure 8A ). The expression of NSs also increased UKL1-induced TBK1 phosphorylation ( Figure 8B ). In summary, these data show that a virus-encoded protein affecting cellular signaling pathways such as NSs can inducibly associate with SINT-speckles.