XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
Is PHOSPHaTIDYLINOSITOL traNSfer aCTIvITY ESSENTIal for
THE fUNCTION of Pdr16p?
Katarína Poloncová, Roman Holič and Peter Griač
Institute of Animal Biochemistry and Genetics SAV, Ivanka pri Dunaji
A common feature of phosphatidylinositol transfer proteins (PITPs) is their ability to
transport phosphatidylinositol (PI) between membranes in vitro. The main PITP of the
yeast Saccharomyces cerevisiae is Sec14p. It is an essential protein that participates in
the vesicular transport from the Golgi membranes. Two point mutations in sites invariably
conserved among all Sec14p homologues present in yeast led to the loss of PI transfer
activity of the Sec14p (Phillips et al. 1999, Molecular Cell 4, p. 187).
Pdr16p is one of the Sec14p homologues with 24% homology of the primary amino acid
sequence to Sec14p. Though the exact function of this protein is yet to be described, it is
known that deletion of the PDR16 gene leads to increased sensitivity to azole antifungals.
Importantly, clinical isolates of Candida albicans and Candida lusitanie resistant to azoles
with increased expression of Pdr16p were identified.
To determine whether the PI transfer activity is essential for the Pdr16p function, we
prepared a mutant that is predicted to be deficient in PI transfer activity of the Pdr16p.
Yeast cells with PI transfer deficient Pdr16p as a sole Pdr16p showed increased sensitivity
to azole antifungals similar to the pdr16Δ cells. Sterol composition of this mutant
was also changed compared to the wt and resembles sterol composition of the pdr16Δ
cells. These data indicate that PI transfer activity of the Pdr16p has to be present for this
protein to fulfill its cellular function.
Acknowledgements: This work was supported by VEGA 2/0077/10 and VVCE-0064-07
grants.
90 XXII. Biochemistry Congress, Martin