Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells
<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>has a predilection for central nervous system infection. <it>C. neoformans </it>traversal of the blood brain barrier, composed of human brain microvascular endothelial cells (H...
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| Format: | Article |
| Language: | English |
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BMC
2012-02-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://www.jbiomedsci.com/content/19/1/19 |
| _version_ | 1811252929802272768 |
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| author | Long Min Huang Sheng-He Wu Chun-Hua Shackleford Gregory M Jong Ambrose |
| author_facet | Long Min Huang Sheng-He Wu Chun-Hua Shackleford Gregory M Jong Ambrose |
| author_sort | Long Min |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>has a predilection for central nervous system infection. <it>C. neoformans </it>traversal of the blood brain barrier, composed of human brain microvascular endothelial cells (HBMEC), is the crucial step in brain infection. However, the molecular mechanism of the interaction between <it>Cryptococcus neoformans </it>and HBMEC, relevant to its brain invasion, is still largely unknown.</p> <p>Methods</p> <p>In this report, we explored several cellular and molecular events involving the membrane lipid rafts and caveolin-1 (Cav1) of HBMEC during <it>C. neoformans </it>infection. Immunofluorescence microscopy was used to examine the roles of Cav1. The knockdown of Cav1 by the siRNA treatment was performed. Phosphorylation of Cav1 relevant to its invasion functions was investigated.</p> <p>Results</p> <p>We found that the host receptor CD44 colocalized with Cav1 on the plasma membrane, and knockdown of Cav1 significantly reduced the fungal ability to invade HBMEC. Although the CD44 molecules were still present, HBMEC membrane organization was distorted by Cav1 knockdown. Concomitantly, knockdown of Cav1 significantly reduced the fungal crossing of the HBMEC monolayer <it>in vitro</it>. Upon <it>C. neoformans </it>engagement, host Cav1 was phosphorylated in a CD44-dependent manner. This phosphorylation was diminished by filipin, a disrupter of lipid raft structure. Furthermore, the phosphorylated Cav1 at the lipid raft migrated inward to the perinuclear localization. Interestingly, the phospho-Cav1 formed a thread-like structure and colocalized with actin filaments but not with the microtubule network.</p> <p>Conclusion</p> <p>These data support that <it>C. neoformans </it>internalization into HBMEC is a lipid raft/caveolae-dependent endocytic process where the actin cytoskeleton is involved, and the Cav1 plays an essential role in <it>C. neoformans </it>traversal of the blood-brain barrier.</p> |
| first_indexed | 2024-04-12T16:42:12Z |
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| id | doaj.art-3bcb2299dde14117b3795c845e942ca4 |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-04-12T16:42:12Z |
| publishDate | 2012-02-01 |
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| spelling | doaj.art-3bcb2299dde14117b3795c845e942ca42022-12-22T03:24:43ZengBMCJournal of Biomedical Science1021-77701423-01272012-02-011911910.1186/1423-0127-19-19Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cellsLong MinHuang Sheng-HeWu Chun-HuaShackleford Gregory MJong Ambrose<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>has a predilection for central nervous system infection. <it>C. neoformans </it>traversal of the blood brain barrier, composed of human brain microvascular endothelial cells (HBMEC), is the crucial step in brain infection. However, the molecular mechanism of the interaction between <it>Cryptococcus neoformans </it>and HBMEC, relevant to its brain invasion, is still largely unknown.</p> <p>Methods</p> <p>In this report, we explored several cellular and molecular events involving the membrane lipid rafts and caveolin-1 (Cav1) of HBMEC during <it>C. neoformans </it>infection. Immunofluorescence microscopy was used to examine the roles of Cav1. The knockdown of Cav1 by the siRNA treatment was performed. Phosphorylation of Cav1 relevant to its invasion functions was investigated.</p> <p>Results</p> <p>We found that the host receptor CD44 colocalized with Cav1 on the plasma membrane, and knockdown of Cav1 significantly reduced the fungal ability to invade HBMEC. Although the CD44 molecules were still present, HBMEC membrane organization was distorted by Cav1 knockdown. Concomitantly, knockdown of Cav1 significantly reduced the fungal crossing of the HBMEC monolayer <it>in vitro</it>. Upon <it>C. neoformans </it>engagement, host Cav1 was phosphorylated in a CD44-dependent manner. This phosphorylation was diminished by filipin, a disrupter of lipid raft structure. Furthermore, the phosphorylated Cav1 at the lipid raft migrated inward to the perinuclear localization. Interestingly, the phospho-Cav1 formed a thread-like structure and colocalized with actin filaments but not with the microtubule network.</p> <p>Conclusion</p> <p>These data support that <it>C. neoformans </it>internalization into HBMEC is a lipid raft/caveolae-dependent endocytic process where the actin cytoskeleton is involved, and the Cav1 plays an essential role in <it>C. neoformans </it>traversal of the blood-brain barrier.</p>http://www.jbiomedsci.com/content/19/1/19<it>Cryptococcus neoformans </it>caveolin-1CD44brain microvascular endothelial cellslipid raft |
| spellingShingle | Long Min Huang Sheng-He Wu Chun-Hua Shackleford Gregory M Jong Ambrose Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells Journal of Biomedical Science <it>Cryptococcus neoformans </it> caveolin-1 CD44 brain microvascular endothelial cells lipid raft |
| title | Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells |
| title_full | Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells |
| title_fullStr | Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells |
| title_full_unstemmed | Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells |
| title_short | Lipid raft/caveolae signaling is required for <it>Cryptococcus neoformans </it>invasion into human brain microvascular endothelial cells |
| title_sort | lipid raft caveolae signaling is required for it cryptococcus neoformans it invasion into human brain microvascular endothelial cells |
| topic | <it>Cryptococcus neoformans </it> caveolin-1 CD44 brain microvascular endothelial cells lipid raft |
| url | http://www.jbiomedsci.com/content/19/1/19 |
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