التفاصيل البيبلوغرافية
| العنوان: |
G2019S LRRK2 modulates Tf recycling in iPSC-derived human microglia. |
| المؤلفون: |
Adamantios Mamais (302600), Jillian H. Kluss (10333635), Luis Bonet-Ponce (336049), Natalie Landeck (414147), Rebekah G. Langston (5740400), Nathan Smith (341990), Alexandra Beilina (139251), Alice Kaganovich (347608), Manik C. Ghosh (11846063), Laura Pellegrini (694179), Ravindran Kumaran (4480765), Ioannis Papazoglou (11846066), George R. Heaton (11846069), Rina Bandopadhyay (302603), Nunziata Maio (11846072), Changyoun Kim (3479372), Matthew J. LaVoie (2287201), David C. Gershlick (11846075), Mark R. Cookson (139260) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Cell Biology, Genetics, Molecular Biology, Neuroscience, Immunology, Cancer, Biological Sciences not elsewhere classified, overexpression cell models, cellular responses downstream, modulating iron uptake, polymorphic lrrk2 variants, lrrk2 kinase substrate, common lrrk2 mutation, +mutations%22">xlink "> mutations, mediated iron uptake, lrrk2 induce sequestration, small gtpase rab8a, postmortem pd tissue, linked lrrk2 mutations, microglia , lrrk2 linked, iron deposition, mediated recycling, induce neurotoxicity, type mice, striatal accumulation, sporadic pd, significant increase, proinflammatory stimuli |
| الوصف: |
(A) iPSC-derived human microglia from WT or G2019S LRRK2 carriers were treated with LPS, and the localization of endogenous Tf and Lamp2 was analyzed by superresolution microscopy and the Imaris Surface render module (A). Partial colocalization between Tf and Lamp2 was observed in control that was significantly decreased with LPS treatment in WT cells but not in G2019S LRRK2 cells that retained lysosomal association of Tf (B) ( N > 12 cells per group from 2 differentiations, one-way ANOVA Tukey post hoc, **** P < 0.0001, F(3,53) = 16.16). G2019S LRRK2 iPSC microglia exhibited larger Tf vesicles compared to WT while LPS treatment induced a decrease in average vesicle size in both cohorts (C) (minimum 3,000 vesicles were counted from 16 cells per group from 2 differentiations, two-way ANOVA, genotype: P < 0.0001, F(1,17753) = 16.38, treatment: P < 0.0001, F(1,17753) = 20.57). LPS treatment induced an increase in the average distance of Tf vesicles from the nucleus in WT cells but that was not significant in G2019S LRRK2 cells (D) (minimum 3,000 vesicles were counted from 16 cells per group from 2 differentiations, two-way ANOVA, genotype: P < 0.0001, F(1,14735) = 104.9, treatment: P < 0.0001, F (1, 14735) = 105.0). The frequency distributions of Tf vesicle proximity to the nucleus were plotted in E and F. The percentage of Tf vesicles proximal to the nucleus was significantly decreased with LPS treatment in WT but not in G2019S LRRK2 cells (E, F) (E: bin at 0.5 μm, two-tailed Student t test; Mann–Whitney U post hoc; ** P = 0.0022; F: bin at 0.5 μm, two-tailed Student t test; Mann–Whitney U post hoc; NS). The underlying data can be found in S1 Data . iPSC, induced pluripotent stem cell; LPS, lipopolysaccharide; LRRK2, leucine-rich repeat kinase 2; Tf, transferrin; WT, wild-type. |
| نوع الوثيقة: |
still image |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/figure/G2019S_LRRK2_modulates_Tf_recycling_in_iPSC-derived_human_microglia_/17222102 |
| DOI: |
10.1371/journal.pbio.3001480.g006 |
| الاتاحة: |
https://doi.org/10.1371/journal.pbio.3001480.g006 |
| Rights: |
CC BY 4.0 |
| رقم الانضمام: |
edsbas.1B7A8D33 |
| قاعدة البيانات: |
BASE |