N-cadherin mediates endocytosis of Candida albicans by endothelial cells

University of California, Los Angeles, Los Ángeles, California, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 04/2005; 280(11):10455-61. DOI: 10.1074/jbc.M412592200
Source: PubMed


Candida albicans is the most common cause of fungal bloodstream infections. To invade the deep tissues, blood-borne organisms must cross the
endothelial cell lining of the vasculature. We have found previously that C. albicans hyphae, but not blastospores, invade endothelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the endothelial cell receptor that mediates the endocytosis
of C. albicans. We determined that endocytosis of C. albicans was not mediated by bridging molecules in the serum and that it was partially dependent on the presence of extracellular
calcium. Using an affinity purification procedure, we discovered that endothelial cell N-cadherin bound to C. albicans hyphae but not blastospores. N-cadherin also co-localized with C. albicans hyphae that were being endocytosed by endothelial cells. Chinese hamster ovary (CHO) cells expressing human N-cadherin endocytosed
significantly more C. albicans hyphae than did CHO cells expressing either human VE-cadherin or no human cadherins. The expression of N-cadherin by the
CHO cells resulted in enhanced endocytosis of hyphae, but not blastospores, indicating the selectivity of the N-cadherin-mediated
endocytosis. Down-regulation of endothelial cell N-cadherin expression with small interfering RNA significantly inhibited
the endocytosis of C. albicans hyphae. Therefore, a novel function of N-cadherin is that it serves as an endothelial cell receptor, which mediates the endocytosis
of C. albicans.

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Available from: Scott G Filler, Apr 22, 2015
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    • "Collectively, these results demonstrate the key role of PDGFRB signaling in the endocytosis of C. albicans. E-cadherin and N-cadherin function as host cell receptors for C. albicans and are required for efficient endocytosis by host cells into epithelial and endothelial cells, respectively (Phan et al. 2005, 2007). We tested whether the decrease in endocytosis that we observe by knockdown of PDGFRB or NEDD9 could be simply the result of reduced expression of the cadherins. "
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    • "Such interactions may also inhibit the interaction between invasins and host cell receptors required to induce endocytosis. Thus, in agreement with the study of Phan et al. (2005), which demonstrated inhibition of endocytosis by serum, it would appear unlikely that serum components act as bridging molecules during interactions with epithelial cells [30]. However, we only observed reduced invasiveness upon treatment with human serum, indicating that invasion-inhibitory factors are host specific and not found in bovine serum. "
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    • "At present it is obvious that Toll-like receptors 2 and 4 and other receptors present on the surface of human immune cells, such as monocytes, macrophages and dendritic cells, are involved in these interactions. Probably some proteins present on the surface of epithelial or endothelial cells, for example N-cadherin, are important for binding of different morphological forms of C. albicans cells, followed by their endocytosis (Phan et al., 2005; Filler, 2006). Due to the ability to bind and invade human endothelial cells C. albicans can traverse the human blood-brain barrier and cause life-threatening meningitis (Jong et al., 2001). "
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