Glycosylphosphatidylinositol (GPI)-anchoring of mamba toxins enables cell-restricted receptor silencing

Katja Näreoja, Lauri M. Louhivuori, Karl E.O. Åkerman, Jussi Meriluoto, Johnny Näsman*

*Korresponderande författare för detta arbete

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

1 Citeringar (Scopus)

Sammanfattning

Muscarinic toxins (MTs) are snake venom peptides found to selectively target specific subtypes of G-protein-coupled receptors. In here, we have attached a glycosylphosphatidylinositol (GPI) tail to three different toxin molecules and evaluated their receptor-blocking effects in a heterologous expression system. MT7-GPI remained anchored to the cell surface and selectively inhibited M 1 muscarinic receptor signaling expressed in the same cell. To further demonstrate the utility of the GPI tail, we generated MT3- and MTα-like gene sequences and fused these to the signal sequence for GPI attachment. Functional assessment of these membrane-anchored toxins on coexpressed target receptors indicated a prominent antagonistic effect. In ligand binding experiments the GPI-anchored toxins were found to exhibit similar selection profiles among receptor subtypes as the soluble toxins. The results indicate that GPI attachment of MTs and related receptor toxins could be used to assess the role of receptor subtypes in specific organs or even cells in vivo by transgenic approaches.

OriginalspråkEngelska
Sidor (från-till)93-97
Antal sidor5
TidskriftBiochemical and Biophysical Research Communications
Volym417
Utgåva1
DOI
StatusPublicerad - 6 jan 2012
MoE-publikationstypA1 Tidskriftsartikel-refererad

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