TMEM16K, a membrane protein carrying 10 transmembrane regions, has phospholipid scramblase activity. TMEM16K is localized to intracellular membranes, but whether it actually scrambles phospholipids inside cells has not been demonstrated, due to technical difficulties in studying intracellular lipid distributions. Here, we developed a freeze-fracture electron microscopy method that enabled us to determine the phosphatidylserine (PtdSer) distribution in the individual leaflets of cellular membranes. Using this method, we found that the endoplasmic reticulum (ER) of mammalian cells harbored abundant PtdSer in its cytoplasmic leaflet and much less in the luminal leaflet, whereas the outer and inner nuclear membranes (NMs) had equivalent amounts of PtdSer in both leaflets. The ER and NMs of budding yeast also harbored PtdSer in their cytoplasmic leaflet, but asymmetrical distribution in the ER was not observed. Treating mouse embryonic fibroblasts with the Ca2+ ionophore A23187 compromised the cytoplasmic leaflet-dominant PtdSer asymmetry in the ER and increased PtdSer in the NMs, especially in the nucleoplasmic leaflet of the inner NM. This Ca2+-induced PtdSer redistribution was not observed in TMEM16K-null fibroblasts, but was recovered in these cells by reexpressing TMEM16K. These results indicate that, similar to the plasma membrane, PtdSer in the ER of mammalian cells is predominantly localized to the cytoplasmic leaflet, and that TMEM16K directly or indirectly mediates Ca2+-dependent phospholipid scrambling in the ER.

No abstract

Darier's disease (DD) is a rare autosomal dominant genodermatosis that results from a pathogenic variant in ATP2A2, the gene that encodes sarco/endoplasmic reticulum ATPase type 2 (SERCA2). 1 Patients usually present with keratotic eruptions in the seborrheic regions that may be vesicular or pustular and are associated with itching and discomfort. Acantholytic dyskeratosis is the characteristic histological feature. Treatment usually involves oral retinoids, which are considered symptomatic rather than curative. 2 DD could be considered a relapsing-remitting disease, and exacerbations are known to occur. Common triggers include heat, sweat, and physical trauma, such as from clothing. Here, we suggest that both COVID-19 infection and COVID-19 vaccination should be considered other common and timely triggers for DD exacerbation. | C A SEA previously healthy 30-year-old man presented to the dermatology clinic with a rash. The patient had noticed slight eruptions about 7 years prior, but was not particularly concerned. However, 6 months before he presented to our clinic this time, his skin eruptions exacerbated and increased in number and size just after his second COVID-19 vaccination (mRNA-1273/Spikevax, Moderna), and he had erythematous maculopapular lesions in large areas of the trunk and extremities. 18 months later, he unfortunately developed a COVID-19 infection, after which his skin symptoms worsened again.Clinical examination found large areas of the upper chest, back, neck, nape, and shins to be affected with erythematous maculopapular eruptions (Figure 1a-c). The papules were approximately 2 mm in diameter and were hyperkeratotic and pigmented. Tiny pustules were also seen.

No abstract

Angiosarcoma of the head and neck (ASHN) is one of the most aggressive malignancies of the skin, but the prognostic factors are not well known because of its rarity. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. In the present retrospective study, we suggest that low plasma fibrinogen levels predict poor prognosis for ASHN.