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ABSTRACT: Introduction
Fungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis.Aim
To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs.Results
Cryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMECs. Blockade with anti-AnxA2 antibody led to a reduction in fungal transcytosis activity but no change in its adhesion efficiency. Intriguingly, AnxA2 depletion caused a significant increase in fungal association activity but had no effect on their transcytosis. AnxA2 suppression resulted in marked reduction in its partner protein S100A10, and S100A10 suppression in BMECs significantly reduced the cryptococcal transcytosis efficiency. Furthermore, AnxA2 dephosphorylation at Tyr23 and dephosphorylation of downstream cofilin were required for cryptococcal transversal of BMECs, both of which might be primarily involved in the association of C. neoformans with host cells.Conclusions
Our work indicated that AnxA2 played complex roles in traversal of C. neoformans across host BMECs, which might be dependent on downstream cofilin to inhibit fungal adhesion but rely on its partner S100A10 to promote cryptococcal transcytosis.
SUBMITTER: Fang W
PROVIDER: S-EPMC6492751 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Fang Wei W Fa Zhen-Zong ZZ Xie Qun Q Wang Gui-Zhen GZ Yi Jiu J Zhang Chao C Meng Guang-Xun GX Gu Ju-Lin JL Liao Wan-Qing WQ
CNS neuroscience & therapeutics 20170128 4
<h4>Introduction</h4>Fungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis.<h4>Aim</h4>To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs.<h4>Results</h4>Cryptococcus neoformans infection initiated upregula ...[more]