A new family of proteins is required for tethering of Casparian strip membrane domain and nutrient homoeostasis in rice.

Cell-cell junctions are essential for multicellular organisms to maintain nutrient homoeostasis. A plant-type tight junction, the Casparian strip (CS)-Casparian strip membrane domain (CSD) that seals the paracellular space between adjacent endodermal cells, has been known for more than one hundred years. However, the molecular basis of this structure remains unknown. Here we report that a new family of proteins containing a glycine/alanine/proline-rich domain, a lectin domain and a secretory signal peptide (GAPLESS) mediates tethering of the plasma membrane to the CS in rice. The GAPLESS proteins are specifically localized in the CS of root endodermal cells, and loss of their functions results in a disabled cell-cell junction and disrupted nutrient homoeostasis. The GAPLESS protein forms a tight complex with OsCASP1 in the plasma membrane, thereby mediating the CS-CSD junction. This study provides valuable insights into the junctional complex of plant endodermal cells, shedding light on our understanding of nutrient homoeostasis in crops and the cell junctions of eukaryotes.

Upregulation of PIK3IP1 monitors the anti-cancer activity of PI3Kα inhibitors in gastric cancer cells.

Gastric cancer remains one of the most malignant cancers in the world. The target-based drugs approved by FDA for gastric cancer treatment include only three targets and benefit a small portion of gastric cancer patients. PIK3CA, a confirmed oncogene, mutates in 7-25% gastric cancer patients. PI3Kα inhibitor BYL719 has been approved for treating specific breast cancer. However, there is no comprehensive study about PI3Kα inhibitor in gastric cancer. In this study, we found pharmacological inhibition or knockdown of PI3Kα effectively inhibited the proliferation of partial gastric cancer cells. Then, we systematically explored the potential biomarkers for predicting or monitoring treatment response according to previous reports and found that basal expression of several receptor tyrosine kinases were related with the sensitivity of gastric cancer cells to BYL719. Next, RNA-seq technique was utilized and showed that BYL719 inhibited Myc targets V2 gene set in sensitive gastric cancer cells, and western blotting further verified that c-Myc was only inhibited in sensitive gastric cancer cells. More importantly, we firstly found BYL719 significantly elevated the expression of PIK3IP1 in sensitive gastric cancer cells, which was also observed in NCI-N87 cell derived xenograft mice models. Meanwhile, knockdown of PIK3IP1 partially rescued the cell growth inhibited by BYL719 in sensitive gastric cancer cells, suggesting the important role of PIK3IP1 in the antitumor activity of BYL719. In conclusion, our study provides biological evidence that PI3Kα is a promising target in specific gastric cancer and the elevation of PIK3IP1 could supply as a biomarker that monitoring treatment response.