ArticleThe Journal of biological chemistry2011
Invasion of Cryptococcus neoformans into human brain microvascular endothelial cells is mediated through the lipid rafts-endocytic pathway via the dual specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 71 citations in OpenAlex.
- PDE4B deficiency aids macrophage differentiation and contributes to Cryptococcus neoformans brain infection.PLoS pathogens · 2026Article
- The Pain Is in the Brain With the Sugar-Coated Killer.The Journal of infectious diseases · 2025Review
- Macropinocytosis mediates neurotropism ofResearch square · 2025Article
- Research progress on immunometabolism and gut microbiota in cryptococcal meningitis: mechanisms and therapeutic implications.Frontiers in neuroscience · 2025Review
- Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis.BMC infectious diseases · 2024Article
- Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024Review
- The pathways and the mechanisms by whichMycology · 2024Review
- Carbohydrates: Binding Sites and Potential Drug Targets for Neural-Affecting Pathogens.Advances in neurobiology · 2023Article
- Macropinocytosis as a potential mechanism driving neurotropism ofFrontiers in cellular and infection microbiology · 2023Review
- A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans.Cell host & microbe · 2022Article
- Host cell membrane microdomains and fungal infection.Cellular microbiology · 2021Review
- Quantitative analysis reveals internalisation of Cryptococcus neoformans by brain endothelial cells in vivo.Cellular microbiology · 2021Article
- Transcriptomic analysis of human brain microvascular endothelial cells exposed to laminin binding protein (adhesion lipoprotein) and Streptococcus pneumoniae.Scientific reports · 2021Article
- Mechanisms of fungal dissemination.Cellular and molecular life sciences : CMLS · 2021Review
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- VCAM1/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection.PLoS pathogens · 2020Article
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- Pathogen interactions with endothelial cells and the induction of innate and adaptive immunity.European journal of immunology · 2018Review
- Cryptococcal Traits Mediating Adherence to Biotic and Abiotic Surfaces.Journal of fungi (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Cryptococcus neoformans is a neurotropic fungal pathogen, which provokes the onset of devastating meningoencephalitis. We used human brain microvascular endothelial cells (HBMEC) as the in vitro model to investigate how C. neoformans traverses across the blood-brain barrier. In this study, we present several lines of evidence indicating that C. neoformans invasion is mediated through the endocytic pathway via lipid rafts. Human CD44 molecules from lipid rafts can directly interact with hyaluronic acid, the C. neoformans ligand. Bikunin, which perturbs CD44 function in the lipid raft, can block C. neoformans adhesion and invasion of HBMEC. The lipid raft marker, ganglioside GM1, co-localizes with CD44 on the plasma membrane, and C. neoformans cells can adhere to the host cell in areas where GM1 is enriched. These findings suggest that C. neoformans entry takes place on the lipid rafts. Upon C. neoformans engagement, GM1 is internalized through vesicular structures to the nuclear membrane. This endocytic redistribution process is abolished by cytochalasin D, nocodazole, or anti-DYRK3 (dual specificity tyrosine-phosphorylation-regulated kinase 3) siRNA. Concomitantly, the knockdown of DYRK3 significantly reduces C. neoformans invasion across the HBMEC monolayer in vitro. Our data demonstrate that the lipid raft-dependent endocytosis process mediates C. neoformans internalization into HBMEC and that the CD44 protein of the hosts, cytoskeleton, and intracellular kinase-DYRK3 are involved in this process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.