SUMMARY Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc), and thus is required for the proper delivery of iron to erythroid progenitors. Snx3 is highly expressed in vertebrate hematopoietic tissues. Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates due to impaired transferrin (Tf)-mediated iron uptake and its accumulation in early endosomes. This impaired iron assimilation can be complemented with non-Tf iron chelates. We show that Snx3 and Vps35, a component of the retromer, interact with Tfrc to sort it to the recycling endosomes. Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism.

Dopaminergic signaling and plasticity are essential to numerous central nervous system functions and pathologies, including movement, cognition and addiction. The amphetamine-and cocaine-sensitive dopamine (DA) transporter (DAT) tightly controls extracellular DA concentrations and half-life. DAT function and surface expression are not static, but are dynamically modulated by membrane trafficking. We recently demonstrated that the DAT carboxy terminus encodes a PKC-sensitive internalization signal that also suppresses basal DAT endocytosis. However, the cellular machinery governing regulated DAT trafficking is not well defined. In work presented here, we identified the Ras-like GTPase, Rin (Rit2) as a protein that interacts with the DAT carboxy terminal endocytic signal. Yeast two-hybrid, GST pulldown and FRET studies establish that DAT and Rin directly interact, and co-localization studies reveal that DAT/Rin associations occur primarily in lipid raft microdomains. Co-immunoprecipitations demonstrate that PKC activation regulates Rin association with DAT. Perturbation of Rin function with GTPase mutants and shRNA-mediated Rin knockdown reveals that Rin is critical for PKC-mediated DAT internalization and functional downregulation. These results establish that Rin is a DAT-interacting protein that is required for PKC-regulated DAT trafficking. Moreover, this work suggests that Rin participates in regulated endocytosis.

Coronavirus disease-19 (COVID-19) is a viral pandemic that started in China and has rapidly expanded worldwide. Typical clinical manifestations include fever, cough and dyspnea after an incubation period of 2-14 days. The diagnosis is based on RT-PCR test through a nasopharyngeal swab. Because of the pulmonary tropism of the virus, pneumonia is often encountered in symptomatic patients. Here, we review the pertinent clinical findings and the current published data describing chest CT findings in COVID-19 pneumonia, the diagnostic performance of CT for diagnosis, including differential diagnosis, as well the evolving role of imaging in this disease. 2. Clinical presentation of COVID-19 COVID-19 can affect all ages; however, the reported median age is lower in the largest Chinese series (47y) [6] compared to the largest American series (63y) [7], with less propensity to affect children (2% of patients were below age 19 in the largest series of 44,672 confirmed cases in China [8]). Asymptomatic cases represent approximately 1% of cases, and can contaminate people around them [8]. Men are overrepresented in COVID-19 cohorts, including in severe cases in series from China (58 %-73 % of the cohorts, 58 %-85 % of severe cases) [6,9] and the US (60.3 % of the largest US cohort, 66.5 % of patients admitted in ICU) [7]. Most people who contract COVID-19 experience mild symptoms and recover without specific treatment. The typical incubation period ranges between 2-7 days, but can be as long as two weeks. The most common symptoms include fever (reported between 43.8 %-98 %), cough (67.8 %-76 %), headache, malaise, myalgia, and dyspnea [6,9,10]. Gastrointestinal symptoms such as abdominal pain and diarrhea have been less frequently reported [6,10-13]. Anosmia and ageusia have also been recently described [14,15]. Several biologic findings have been reported: lymphopenia, elevated inflammatory indices such as C-reactive protein (CRP), D-dimer, procalcitonin and ferritin, lactate dehydrogenase (LDH) and interleukin-6 (IL-6); IL-6 in particular may identify cases with poor

No abstract

No abstract