Australian scorpion Hormurus waigiensis venom fractions show broad bioactivity through modulation of bio-impedance and cytosolic calcium

Journal Publication ResearchOnline@JCU
Housley, David M.;Pinyon, Jeremy L.;Jonquieres, Georg von;Perera, Chamini J.;Smout, Michael;Liddell, Michael J.;Jennings, Ernest A.;Wilson, David;Housley, Gary D.
Abstract

Scorpion venoms are a rich source of bioactive molecules, but characterisation of toxin peptides affecting cytosolic Ca2+, central to cell signalling and cell death, is limited. We undertook a functional screening of the venom of the Australian scorpion Hormurus waigiensis to determine the breadth of Ca2+ mobilisation. A human embryonic kidney (HEK293) cell line stably expressing the genetically encoded Ca2+ reporter GCaMP5G and the rabbit type 1 ryanodine receptor (RyR1) was developed as a biosensor. Size-exclusion Fast Protein Liquid Chromatography separated the venom into 53 fractions, constituting 12 chromatographic peaks. Liquid chromatography mass spectroscopy identified 182 distinct molecules with 3 to 63 components per peak. The molecular weights varied from 258 Da—13.6 kDa, with 53% under 1 kDa. The majority of the venom chromatographic peaks (tested as six venom pools) were found to reversibly modulate cell monolayer bioimpedance, detected using the xCELLigence platform (ACEA Biosciences). Confocal Ca2+ imaging showed 9/14 peak samples, with molecules spanning the molecular size range, increased cytosolic Ca2+ mobilization. H. waigiensis venom Ca2+ activity was correlated with changes in bio-impedance, reflecting multi-modal toxin actions on cell physiology across the venom proteome.

Journal

Biomolecules

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Volume

10

ISBN/ISSN

2218-273X

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Issue

4

Pages Count

17

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Publisher

MDPI

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DOI

10.3390/biom10040617