HAI-2 stabilizes, inhibits, and regulates SEA-cleavage-dependent secretory transport of matriptase

It has recently been shown that HAI-2 is able to suppress carcinogenesis induced by overexpression of matriptase, as well as cause regression of individual established tumors in a mouse model system. However, the role of HAI-2 is poorly understood. In the present study we describe three mutations in the binding loop of the HAI-2 Kunitz domain 1 (K42N, C47F, and R48L) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non-SEA domain cleaved matriptase in the ER. We suggest that, like other known SEA domains, the matriptase SEA domain auto-cleaves and reflects that correct oligomerization, maturation, and/or folding has been obtained. Our results suggest that the HAI-2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation, and/or folding of matriptase, and as a result the SEA domain cleavage of matriptase. Two of the HAI-2 Kunitz domain 1 mutants investigated (C47F, R48L, C47F/R48L) also displayed a reduced ability to proteolytically silence matriptase. Hence, HAI-2 separately stabilizes matriptase, regulates the secretory transport, possibly via maturation/oligomerization, and inhibits the proteolytic activity of matriptase in the ER, and possible throughout the secretory pathway

First Sagittarius A* Event Horizon Telescope Results. VII. Polarization of the Ring

The Event Horizon Telescope observed the horizon-scale synchrotron emission region around the Galactic center supermassive black hole, Sagittarius A* (Sgr A*), in 2017. These observations revealed a bright, thick ring morphology with a diameter of 51.8 ± 2.3 μas and modest azimuthal brightness asymmetry, consistent with the expected appearance of a black hole with mass M ≈ 4 × 106 M ⊙. From these observations, we present the first resolved linear and circular polarimetric images of Sgr A*. The linear polarization images demonstrate that the emission ring is highly polarized, exhibiting a prominent spiral electric vector polarization angle pattern with a peak fractional polarization of ∼40% in the western portion of the ring. The circular polarization images feature a modestly (∼5%–10%) polarized dipole structure along the emission ring, with negative circular polarization in the western region and positive circular polarization in the eastern region, although our methods exhibit stronger disagreement than for linear polarization. We analyze the data using multiple independent imaging and modeling methods, each of which is validated using a standardized suite of synthetic data sets. While the detailed spatial distribution of the linear polarization along the ring remains uncertain owing to the intrinsic variability of the source, the spiraling polarization structure is robust to methodological choices. The degree and orientation of the linear polarization provide stringent constraints for the black hole and its surrounding magnetic fields, which we discuss in an accompanying publication