ArticleThe Journal of biological chemistry2012
Cryptococcus neoformans activates RhoGTPase proteins followed by protein kinase C, focal adhesion kinase, and ezrin to promote traversal across the blood-brain barrier.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies.Frontiers in pharmacology · 2026Review
- Reconsidering the blood-brain barrier: histopathology and microanatomy of cryptococcal CNS infection.Microbiology and molecular biology reviews : MMBR · 2025Review
- Normal opening pressure lumbar puncture in cryptococcal meningitis complicated by a cerebral venous thrombosis: a case report and literature review.Frontiers in medicine · 2025Article
- Inhibition of RhoA Prevents Cryptococcus neoformans Capsule Glucuronoxylomannan-Stimulated Brain Endothelial Barrier Disruption.The Journal of infectious diseases · 2024Article
- Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024Review
- Article
- The pathways and the mechanisms by whichMycology · 2024Review
- Glucuronoxylomannan intranasal challenge prior to Cryptococcus neoformans pulmonary infection enhances cerebral cryptococcosis in rodents.PLoS pathogens · 2023Article
- Macropinocytosis as a potential mechanism driving neurotropism ofFrontiers in cellular and infection microbiology · 2023Review
- Comparative miRNA transcriptomics of macaques and mice revealsEmerging microbes & infections · 2022Article
- Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Host cell membrane microdomains and fungal infection.Cellular microbiology · 2021Review
- Mechanisms of fungal dissemination.Cellular and molecular life sciences : CMLS · 2021Review
- KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway.Frontiers in oncology · 2021Article
- Dangerous Liaisons: Interactions ofPathogens (Basel, Switzerland) · 2020Review
- MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration.Journal of cellular and molecular medicine · 2019Article
- A streptococcal Fic domain-containing protein disrupts blood-brain barrier integrity by activating moesin in endothelial cells.PLoS pathogens · 2019Article
- Cryptococcal Meningitis and Anti-virulence Therapeutic Strategies.Frontiers in microbiology · 2019Review
- Cryptococcal Traits Mediating Adherence to Biotic and Abiotic Surfaces.Journal of fungi (Basel, Switzerland) · 2018Review
- The blood-brain barrier internalises Cryptococcus neoformans via the EphA2-tyrosine kinase receptor.Cellular microbiology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. Previous studies have demonstrated that Cryptococcus binding and invasion of human brain microvascular endothelial cells (HBMEC) is a prerequisite for transmigration across the blood-brain barrier. However, the molecular mechanism involved in the cryptococcal blood-brain barrier traversal is poorly understood. In this study we examined the signaling events in HBMEC during interaction with C. neoformans. Analysis with inhibitors revealed that cryptococcal association, invasion, and transmigration require host actin cytoskeleton rearrangement. Rho pulldown assays revealed that Cryptococcus induces activation of three members of RhoGTPases, e.g. RhoA, Rac1, and Cdc42, and their activations are required for cryptococcal transmigration across the HBMEC monolayer. Western blot analysis showed that Cryptococcus also induces phosphorylation of focal adhesion kinase (FAK), ezrin, and protein kinase C α (PKCα), all of which are involved in the rearrangement of host actin cytoskeleton. Down-regulation of FAK, ezrin, or PKCα by shRNA knockdown, dominant-negative transfection, or inhibitors significantly reduces cryptococcal ability to traverse the HBMEC monolayer, indicating their positive role in cryptococcal transmigration. In addition, activation of RhoGTPases is the upstream event for phosphorylation of FAK, ezrin, and PKCα during C. neoformans-HBMEC interaction. Taken together, our findings demonstrate that C. neoformans activates RhoGTPases and subsequently FAK, ezrin, and PKCα to promote their traversal across the HBMEC monolayer, which is the critical step for cryptococcal brain infection and development of meningitis.
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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.