The virally encoded fungal toxin KP4 specifically blocks L-type voltage-gated calcium channels

Matthew J. Gage, Stanley G. Rane, Gregory H. Hockerman, Thomas Smith

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis. Previous studies demonstrated that this toxin inhibits growth of the target fungal cells by blocking calcium uptake rather than forming channels, as had been suggested previously. Unexpectedly, this toxin was also shown to inhibit voltage-gated calcium channel activity in mammalian cells. We used whole-cell patch-clamp techniques to further characterize this activity against mammalian cells, KP4 is shown to specifically block L-type calcium channels with weak voltage dependence to the block, Because KP4 activity is abrogated by calcium, KP4 probably binds competitively with calcium to the channel exterior. Finally, it is shown that chemical reagents that modify lysine residues reduce KP4 activity in both patch-clamp experiments on mammalian cells and in fungal killing assays. Because the only lysine residue is K42, this residue seems to be crucial for both mammalian and fungal channel activity. Our results defining the type of mammalian channel affected by this fungal toxin further support our contention that KP4 inhibits fungal growth by blocking transmembrane calcium flux through fungal calcium channels, and imply a high degree of structural homology between these fungal and mammalian calcium channels.

Original languageEnglish (US)
Pages (from-to)936-944
Number of pages9
JournalMolecular Pharmacology
Volume61
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

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Mycotoxins
Calcium Channels
Calcium
Lysine
Ustilago
L-Type Calcium Channels
Patch-Clamp Techniques
Growth

ASJC Scopus subject areas

  • Pharmacology

Cite this

The virally encoded fungal toxin KP4 specifically blocks L-type voltage-gated calcium channels. / Gage, Matthew J.; Rane, Stanley G.; Hockerman, Gregory H.; Smith, Thomas.

In: Molecular Pharmacology, Vol. 61, No. 4, 2002, p. 936-944.

Research output: Contribution to journalArticle

Gage, Matthew J. ; Rane, Stanley G. ; Hockerman, Gregory H. ; Smith, Thomas. / The virally encoded fungal toxin KP4 specifically blocks L-type voltage-gated calcium channels. In: Molecular Pharmacology. 2002 ; Vol. 61, No. 4. pp. 936-944.
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