Type Iγ phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with μ1B adaptin

Assembly of E-cadherin–based adherens junctions (AJ) is obligatory for establishment of polarized epithelia and plays a key role in repressing the invasiveness of many carcinomas. Here we show that type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) directly binds to E-cadherin and modulates E-cadherin trafficking. PIPKIγ also interacts with the μ subunits of clathrin adaptor protein (AP) complexes and acts as a signalling scaffold that links AP complexes to E-cadherin. Depletion of PIPKIγ or disruption of PIPKIγ binding to either E-cadherin or AP complexes results in defects in E-cadherin transport and blocks AJ assembly. An E-cadherin germline mutation that loses PIPKIγ binding and shows disrupted basolateral membrane targeting no longer forms AJs and leads to hereditary gastric cancers. These combined results reveal a novel mechanism where PIPKIγ serves as both a scaffold, which links E-cadherin to AP complexes and the trafficking machinery, and a regulator of trafficking events via the spatial generation of phosphatidylinositol-4,5-bisphosphate

Vector Overhauser magnetometer POS-4: experience and prospects of application

The results of practical use of a POS-4 vector magnetometer, developed by the Research Laboratory of Quantum Magnetometry, UrFU (Yekaterinburg) and based on POS Overhauser sensors, are presented. Continuous measurements by POS-4 have been carried out at the Paratunka observatory (IKIR FEB RAS, Kamchatka) since 2015, were done at the Saint Petersburg observatory (GC RAS / IZMIRAN SPb Branch, Leningrad Region) in 2017-2018 and have been performed at the Arti observatory (Institute of Geophysics, UB RAS, Sverdlovsk Region) since 2020. On the new high-latitude observatory White Sea (IAGA code WSE, GC RAS / MSU, Nikolai Pertsov White Sea Biological Station , Karelia), POS-4 is used as a main variometer for magnetic measurements. In April 2019, the magnetometer was successfully used for field measurements on ice during the TRANSARCTIC expedition in the Barents Sea (AARI, Roshydromet). At the beginning of 2021 IZMIRAN started testing two POS-4 magnetometers at the Moskow observatory. According to the results of field and observatory measurements it was possible to identify the advantages and disadvantages of the magnetometer and provide the information for its developers for further modernization in order to improve its efficiency and reliability. Many years of experience in POS-4 application determine the areas where its scientific and applied usage will provide important results, for example, for magnetic measurements in the Arctic regions or for monitoring of active zones around volcanoes

Subcellular Localization of Activated AKT in Estrogen Receptor- and Progesterone Receptor-Expressing Breast Cancers : Potential Clinical Implications

Activated v-AKT murine thymoma viral oncogene homolog 1 (AKT)/protein kinase B (PKB) kinase (pAKT) is localized to the plasma membrane, cytoplasm, and/or nucleus in 50% of cancers. The clinical importance of pAKT localization and the mechanism(s) controlling this compartmentalization are unknown. In this study, we examined nuclear and cytoplasmic phospho-AKT (pAKT) expression by immunohistochemistry in a breast cancer tissue microarray (n = 377) with ≈15 years follow-up and integrated these data with the expression of estrogen receptor (ER)α, progesterone receptor (PR), and FOXA1. Nuclear localization of pAKT (nuclear-pAKT) was associated with long-term survival (P = 0.004). Within the ERα+/PR+ subgroup, patients with nuclear-pAKT positivity had better survival than nuclear-pAKT–negative patients (P ≤ 0.05). The association of nuclear-pAKT with the ERα+/PR+ subgroup was validated in an independent cohort (n = 145). TCL1 family proteins regulate nuclear transport and/or activation of AKT. TCL1B is overexpressed in ERα-positive compared with ERα-negative breast cancers and in lung metastasis–free breast cancers. Therefore, we examined the possible control of TCL1 family member(s) expression by the estrogen:ERα pathway. Estradiol increased TCL1B expression and increased nuclear-pAKT levels in breast cancer cells; short- interfering RNA against TCL1B reduced nuclear-pAKT. Overexpression of nuclear-targeted AKT1 in MCF-7 cells increased cell proliferation without compromising sensitivity to the anti-estrogen, tamoxifen. These results suggest that subcellular localization of activated AKT plays a significant role in determining its function in breast cancer, which in part is dependent on TCL1B expression