%0 Journal Article
%T Lipid raft/caveolae signaling is required for Cryptococcus neoformans invasion into human brain microvascular endothelial cells
%A Min Long
%A Sheng-He Huang
%A Chun-Hua Wu
%A Gregory M Shackleford
%A Ambrose Jong
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-19
%X In this report, we explored several cellular and molecular events involving the membrane lipid rafts and caveolin-1 (Cav1) of HBMEC during C. neoformans 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.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 in vitro. Upon C. neoformans 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.These data support that C. neoformans 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 C. neoformans traversal of the blood-brain barrier.Cryptococcus neoformans is commonly found in the environment, such as in the soil and in bird droppings. These fungal cells may be inhaled and deposited into the lungs and into the blood stream, providing a path for C. neoformans to reach the brain. In the case of the immunocompromised, this fungus could cause life-threatening cryptococcal meningitis [1,2]. In the world today, cryptococcal infection has become the most common fungal pathogen of the central nervous system [3]. In order to cause meningoencephalitis, the fungal cells must cross the blood-brain barrier (BBB). A speci
%K Cryptococcus neoformans
%K caveolin-1
%K CD44
%K brain microvascular endothelial cells
%K lipid raft
%U http://www.jbiomedsci.com/content/19/1/19