title: Complex Roles of Annexin A2 in Host Blood-Brain Barrier Invasion by Cryptococcus neoformans.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: PLA Key Laboratory of Mycosis, Department of Dermatology and Venereology, Changzheng Hospital, Shanghai, China.|Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Institute of Medical Mycology, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Institute of Medical Mycology, Second Military Medical University, Shanghai, China.
authors.forename: Zhen-Zong
authors.initials: ZZ
authors.lastname: Fa
authors.affiliation: Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: ICU Department, Urumuqi Army General Hospital, Urumqi, Xinjiang, China.
authors.forename: Gui-Zhen
authors.initials: GZ
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Institute of Medical Mycology, Second Military Medical University, Shanghai, China.
authors.forename: Jiu
authors.initials: J
authors.lastname: Yi
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Institute of Medical Mycology, Second Military Medical University, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guang-Xun
authors.initials: GX
authors.lastname: Meng
authors.affiliation: PLA Key Laboratory of Mycosis, Department of Dermatology and Venereology, Changzheng Hospital, Shanghai, China.|Department of Dermatology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ju-Lin
authors.initials: JL
authors.lastname: Gu
authors.affiliation: Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai Institute of Medical Mycology, Second Military Medical University, Shanghai, China.
authors.forename: Wan-Qing
authors.identifier: http://orcid.org/0000-0002-0303-1393
authors.initials: WQ
authors.lastname: Liao
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000906:Antibodies / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D001921:Brain / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology; D003455:Cryptococcus neoformans; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D013997:Time Factors; D057900:Transcytosis / Q000187:drug effects / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D000099248:S100 Calcium Binding Protein A10
chemical_list: D051339:Actin Depolymerizing Factors; D017306:Annexin A2; D000906:Antibodies; D002614:Chelating Agents; D004533:Egtazic Acid; D011743:Pyrimidines; D034741:RNA, Small Interfering; D009418:S100 Proteins; D014443:Tyrosine; D000099248:S100 Calcium Binding Protein A10; C412373:AG 1879; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
keywords: Annexin A2; Blood-Brain Barrier; Cofilin; Cryptococcal meningitis