Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy.

Syk is a cytoplasmic kinase that serves multiple functions within the immune system to couple receptors for antigens and antigen-antibody complexes to adaptive and innate immune responses. Recent studies have identified additional roles for the kinase in cancer cells, where its expression can either promote or suppress tumor cell growth, depending on the context. Proteomic analyses of Syk-binding proteins identified several interacting partners also found to be recruited to stress granules. We show here that the treatment of cells with inducers of stress granule formation leads to the recruitment of Syk to these protein-RNA complexes. This recruitment requires the phosphorylation of Syk on tyrosine and results in the phosphorylation of proteins at or near the stress granule. Grb7 is identified as a Syk-binding protein involved in the recruitment of Syk to the stress granule. This recruitment promotes the formation of autophagosomes and the clearance of stress granules from the cell once the stress is relieved, enhancing the ability of cells to survive the stress stimulus.

Longitudinal SARS-CoV-2 antibody study using the Easy Check COVID-19 IgM/IgG™ lateral flow assay.

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body's temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31-60 days PSO. By 61-90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1-4 days PSO with 86% positivity observed at 5-7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection.

A Mouse Model for the Study of SYK Function through Chemical Genetics Demonstrates SYK-Dependent Signaling through the B Cell Receptor, but Not TLR4.

The SYK protein-tyrosine kinase is a well-known mediator of signals elicited by the clustering of BCR complexes and other receptors that bear components that contain one or more ITAM sequences. Additional roles for the kinase in signaling through other receptor classes also have been described. To assist in the identification of SYK-regulated processes, we developed mice lacking endogenous Syk genes but containing instead genes coding for an analogue-sensitive form of SYK (SYK-AQL). SYK-AQL supports the development of B cells, and these can be activated with both anti-IgM F(ab')2 through the BCR and LPS through TLR4. An orthogonal inhibitor that selectively targets SYK-AQL blocks the activation of B cells by anti-IgM F(ab')2 in SYK-AQL-expressing but not wild-type cells. The SYK-AQL-specific inhibitor, however, does not block B cell activation in response to LPS in either wild-type or SYK-AQL-expressing cells. Thus, SYK is essential for coupling the BCR but not TLR4 to the activation of B cells.