The CbbQO-type rubisco activases encoded in carboxysome gene clusters can activate carboxysomal form IA rubiscos

The CO₂-fixing enzyme rubisco is responsible for almost all carbon fixation. This process frequently requires rubisco activase (Rca) machinery, which couples ATP hydrolysis to the removal of inhibitory sugar phosphates, including the rubisco substrate ribulose 1,5-bisphosphate (RuBP). Rubisco is sometimes compartmentalized in carboxysomes, bacterial microcompartments that enable a carbon dioxide concentrating mechanism (CCM). Characterized carboxysomal rubiscos, however, are not prone to inhibition, and often no activase machinery is associated with these enzymes. Here, we characterize two carboxysomal rubiscos of the form IA^C clade that are associated with CbbQO-type Rcas. These enzymes release RuBP at a much lower rate than the canonical carboxysomal rubisco from Synechococcus PCC6301. We found that CbbQO-type Rcas encoded in carboxysome gene clusters can remove RuBP and the tight-binding transition state analog carboxy-arabinitol 1,5-bisphosphate from cognate rubiscos. The Acidithiobacillus ferrooxidans genome encodes two form IA rubiscos associated with two sets of cbbQ and cbbO genes. We show that the two CbbQO activase systems display specificity for the rubisco enzyme encoded in the same gene cluster, and this property can be switched by substituting the C-terminal three residues of the large subunit. Our findings indicate that the kinetic and inhibitory properties of proteobacterial form IA rubiscos are diverse and predict that Rcas may be necessary for some α-carboxysomal CCMs. These findings will have implications for efforts aiming to introduce biophysical CCMs into plants and other hosts for improvement of carbon fixation of crops.     

Integration of single cell data by disentangled representation learning

Recent developments of single cell RNA-sequencing technologies lead to the exponential growth of single cell sequencing datasets across different conditions. Combining these datasets helps to better understand cellular identity and function. However, it is challenging to integrate different datasets from different laboratories or technologies due to batch effect, which are interspersed with biological variances. To overcome this problem, we have proposed Single Cell Integration by Disentangled Representation Learning (SCIDRL), a domain adaption-based method, to learn low-dimensional representations invariant to batch effect. This method can efficiently remove batch effect while retaining cell type purity. We applied it to thirteen diverse simulated and real datasets. Benchmark results show that SCIDRL outperforms other methods in most cases and exhibits excellent performances in two common situations: (i) effective integration of batch-shared rare cell types and preservation of batch-specific rare cell types; (ii) reliable integration of datasets with different cell compositions. This demonstrates SCIDRL will offer a valuable tool for researchers to decode the enigma of cell heterogeneity.     

The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.     

Estrogen receptor beta promotes lung cancer invasion via increasing CXCR4 expression

Lung cancer is one of the most lethal malignant tumors in the world. The high recurrence and mortality rate make it urgent for scientists and clinicians to find new targets for better treatment of lung cancer. Early studies indicated that estrogen receptor β (ERβ) might impact the progression of non-small-cell lung cancer (NSCLC). However, the detailed mechanisms, especially its linkage to the CXCR4-mediated cell invasion, remain unclear. Here we found that ERβ could promote NSCLC cell invasion via increasing the circular RNA (circRNA), circ-TMX4, expression via directly binding to the 5′ promoter region of its host gene TMX4. ERβ-promoted circ-TMX4 could then sponge and inhibit the micro RNA (miRNA, miR), miR-622, expression, which can then result in increasing the CXCR4 messenger RNA translation via a reduced miRNA binding to its 3′ untranslated region (3′UTR). The preclinical study using an in vivo mouse model with orthotopic xenografts of NSCLC cells confirmed the in vitro data, and the human NSCLC database analysis and tissue staining also confirmed the linkage of ERβ/miR-622/CXCR4 signaling to the NSCLC progression. Together, our findings suggest that ERβ can promote NSCLC cell invasion via altering the ERβ/circ-TMX4/miR-622/CXCR4 signaling, and targeting this newly circ-TMX4/miR-622/CXCR4 signaling may help us find new treatment strategies to better suppress NSCLC progression.Subject terms: Non-small-cell lung cancer, Metastasis