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Invasion of Cryptococcus neoformans into human brain microvascular endothelial cells requires protein kinase C-alpha

Ambrose Jong1, Chun-Hua Wu, Nemani V Prasadarao

  • 1Division of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA. ajong@chla.usc.edu

Cellular Microbiology
|May 21, 2008
PubMed

Insights

Protein kinase C alpha (PKCalpha) is crucial for Cryptococcus neoformans invasion of the blood-brain barrier. Inhibiting PKCalpha or its downstream actin filament activity blocks fungal entry into brain endothelial cells.

Area of Science:

  • Mycology
  • Neuroscience
  • Cell Biology

Background:

  • Cryptococcus neoformans causes meningoencephalitis by crossing the blood-brain barrier (BBB).
  • Previous work identified the CPS1 gene's role in fungal adherence to human brain microvascular endothelial cells (HBMEC).

Purpose of the Study:

  • To investigate the role of protein kinase C (PKC) signaling in C. neoformans invasion of the BBB.

Main Methods:

  • Utilized a PKC inhibitor (G109203X) and dominant-negative PKCalpha to block fungal invasion.
  • Assessed PKCalpha phosphorylation and enzymatic activity in infected HBMEC.
  • Employed immunofluorescence microscopy and cytochalasin D to examine actin filament dynamics.

Main Results:

  • PKC inhibition and dominant-negative PKCalpha blocked C. neoformans invasion of HBMEC.
  • PKCalpha phosphorylation and activity were induced during fungal infection.
  • PKCalpha colocalized with beta-actin, and its inhibition attenuated actin filament activity.

Conclusions:

  • PKCalpha plays a critical role in C. neoformans invasion of HBMEC.
  • Downstream actin filament activity is essential for this fungal invasion process.

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