Recycling is a limiting step for receptor-mediated endocytosis. We first report three in vitro or in vivo evidences that class III PI3K/VPS34 is the key PI3K isoform regulating apical recycling. A substractive approach, comparing in Opossum Kidney (OK) cells a pan-class I/II/III PI3K inhibitor (LY294002) with a class I/II PI3K inhibitor (ZSTK474), suggested that class III PI3K/VPS34 inhibition induced selective apical endosome swelling and sequestration of the endocytic receptor, megalin/LRP-2, causing surface down-regulation. GFP-(FYVE)x2 overexpression to sequester PI(3)P caused undistinguishable apical endosome swelling. In mouse kidney proximal tubular cells, conditional Vps34 inactivation also led to vacuolation and intracellular megalin redistribution. We next report that removal of LY294002 from LY294002-treated OK cells induced a spectacular burst of recycling tubules and restoration of megalin surface pool. Acute triggering of recycling tubules revealed recruitment of dynamin-GFP and dependence of dynamin-GTPase, guidance directionality by microtubules, and suggested that a microfilamentous net constrained endosomal swelling. We conclude that (i) besides its role in endosome fusion, PI3K-III is essential for endosome fission/recycling; and (ii) besides its role in endocytic entry, dynamin also supports tubulation of recycling endosomes. The unleashing of recycling upon acute reversal of PI3K inhibition may help study its dynamics and associated machineries.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/tra.12079 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Accuracy of cephalometric landmark and cephalometric analysis from lateral facial photograph by using CNN-based algorithm.
Sci Rep
December 2024
Department of Orthodontics, Tokyo Dental College, 2-9-18, Kandamisaki-Cho, Chiyoda- Ku, Tokyo, 101-006, Japan.
Cephalometric analysis is the primary diagnosis method in orthodontics. In our previous study, the algorithm was developed to estimate cephalometric landmarks from lateral facial photographs of patients with normal occlusion. This study evaluates the estimation accuracy by the algorithm trained on a dataset of 2320 patients with added malocclusion patients and the analysis values.
View Article and Find Full Text PDFThree-dimensional assessment of mandibular canal in different sagittal and growth patterns for safe placement of temporary skeletal anchorage devices: A prospective study.
Am J Orthod Dentofacial Orthop
December 2024
Department of Orthodontics, Teerthanker Mahavir Dental College and Research Centre, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India.
Introduction: The primary objective of this study was to assess the 3-dimensional position of the mandibular canal (MC) in different craniofacial patterns to know about the safe placement of temporary skeletal anchorage devices using cone-beam computed tomography (CBCT). The secondary objectives were to assess sex differences and correlate the MC position with various factors.
Methods: This prospective, observational study was conducted on 90 patients, divided into 3 groups based on the sagittal pattern: skeletal Class I, Class II, and Class III.
HLA Class I and II Alleles in Anti-Acetylcholine Receptor Antibodies Positive and Double-Seronegative Myasthenia Gravis Patients of Romanian Descent.
Neurol Int
December 2024
Department of Immunology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania.
: Several significant associations between certain Human Leukocyte Antigen (HLA) alleles and myasthenia gravis (MG) subtypes were established in populations from Western Europe and North America and, to a lesser extent, from China and Japan. However, such data are scarcely available for Eastern Europe. This study aimed to analyze the associations of HLA Class I and II alleles with MG and its serological subtypes (with anti-acetylcholine receptor autoantibodies, RAch+MG, and double-seronegative, dSNMG) in myasthenic patients of Romanian descent.
View Article and Find Full Text PDFLong-Term Outcome of Elderly Patients with Severe Aortic Stenosis Undergoing a Tailored Interventional Treatment Using Frailty-Based Management: Beyond the Five-Year Horizon.
J Pers Med
December 2024
Cardiology Unit, Ospedale del Cuore, Fondazione Toscana "G. Monasterio", 54100 Massa, Italy.
Elderly patients with severe aortic stenosis (AS) need individualized decision-making in their management in order to benefit in terms of survival and improvement of quality of life. Frailty, a common condition in elderly patients, needs to be considered when weighing treatment options. We aimed to evaluate outcomes including survival and functional parameters according to disability criteria at six years of follow-up in an older population treated for severe AS using a frailty-based management.
View Article and Find Full Text PDFTwo-fold increased risk of cardiovascular events in people with MDR HIV: a matched cohort analysis with data from the PRESTIGIO registry.
J Antimicrob Chemother
December 2024
Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Background: Major adverse cardiovascular events (MACEs) may contribute to the high morbidity in people with four-class drug-resistant HIV (4DR-PWH).
Objectives: To explore the probability of MACEs in 4DR-PWH compared with non-4DR controls.
Methods: This was a retrospective, propensity score-matched cohort study on 4DR-PWH (cases) and non-4DR-PWH (controls), on ART, without previous MACEs.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!