Modulating intracellular pathways to improve non-viral delivery of RNA therapeutics

T Van de Vyver, SC De Smedt, K Raemdonck - Advanced Drug Delivery …, 2022 - Elsevier
RNA therapeutics (eg siRNA, oligonucleotides, mRNA, etc.) show great potential for the
treatment of a myriad of diseases. However, to reach their site of action in the cytosol or …

Endomembrane tension and trafficking

A Saric, SA Freeman - Frontiers in Cell and Developmental Biology, 2021 - frontiersin.org
Eukaryotic cells employ diverse uptake mechanisms depending on their specialized
functions. While such mechanisms vary widely in their defining criteria: scale, molecular …

Proton-gated anion transport governs macropinosome shrinkage

M Zeziulia, S Blin, FW Schmitt, M Lehmann… - Nature Cell …, 2022 - nature.com
Intracellular organelles change their size during trafficking and maturation. This requires the
transport of ions and water across their membranes. Macropinocytosis, a ubiquitous form of …

The chloride antiporter CLCN7 is a modifier of lysosome dysfunction in FIG4 and VAC14 mutants

X Cao, GM Lenk, V Mikusevic, JA Mindell… - Plos Genetics, 2023 - journals.plos.org
The phosphatase FIG4 and the scaffold protein VAC14 function in the biosynthesis of PI (3,
5) P2, a signaling lipid that inhibits the lysosomal chloride transporter ClC-7. Loss-of …

GCAF (TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway

W Zhang, X Yang, Y Li, L Yu, B Zhang, J Zhang… - Nature …, 2022 - nature.com
Abstract The mannose-6-phosphate (M6P) biosynthetic pathway for lysosome biogenesis
has been studied for decades and is considered a well-understood topic. However, whether …

Improving gene function predictions using independent transcriptional components

CG Urzúa-Traslaviña, VC Leeuwenburgh… - Nature …, 2021 - nature.com
The interpretation of high throughput sequencing data is limited by our incomplete functional
understanding of coding and non-coding transcripts. Reliably predicting the function of such …

Genome-scale CRISPR screening at high sensitivity with an empirically designed sgRNA library

L Henkel, B Rauscher, B Schmitt, J Winter, M Boutros - BMC biology, 2020 - Springer
Background In recent years, large-scale genetic screens using the CRISPR/Cas9 system
have emerged as scalable approaches able to interrogate gene function with …

Click chemistry–enabled CRISPR screening reveals GSK3 as a regulator of PLD signaling

TW Bumpus, S Huang, R Tei… - Proceedings of the …, 2021 - National Acad Sciences
Enzymes that produce second messengers are highly regulated. Revealing the mechanisms
underlying such regulation is critical to understanding both how cells achieve specific …

Tonic inhibition of the chloride/proton antiporter ClC-7 by PI (3, 5) P2 is crucial for lysosomal pH maintenance

X Leray, JK Hilton, K Nwangwu, A Becerril, V Mikusevic… - Elife, 2022 - elifesciences.org
The acidic luminal pH of lysosomes, maintained within a narrow range, is essential for
proper degrative function of the organelle and is generated by the action of a V-type H+ …

Renal deletion of LRRC8/VRAC channels induces proximal tubulopathy

KI López-Cayuqueo, R Planells-Cases… - Journal of the …, 2022 - journals.lww.com
Background Volume-regulated anion channels (VRACs) are heterohexamers of LRRC8A
with LRRC8B,-C,-D, or-E in various combinations. Depending on the subunit composition …