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Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans.


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

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Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans.

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]

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