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International Journal of Toxicology
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Effect of Maitotoxin on Guanine Nucleotide Interaction With G-Protein {alpha} Subunits

Ritindra N. Khan

Department of Biology, Armstrong Atlantic State University, Savannah, Georgia, USA

Edward G. Tall

Departments of Anesthesiology and Physiology and Biophysics, School of Medicine, State University of New York, Stony Brook, New York, USA

Mario Rebecchi

Departments of Anesthesiology and Physiology and Biophysics, School of Medicine, State University of New York, Stony Brook, New York, USA

John S. Ramsdell

NOAA, Center for Coastal Environmental Health and Biomolecular Research, Marine Biotoxins Program, Charleston, South Carolina, USA

Srinivas Pentyala

Departments of Anesthesiology and Physiology and Biophysics, School of Medicine, State University of New York, Stony Brook, New York, USA

Maitotoxin is a potent water-soluble polyether toxin produced by the marine dinoflagellate Gambierdiscus toxicus. Although associated with increased calcium uptake, mobilization of internal calcium stores, and enhanced phosphoinositide metabolism, the primary molecular mechanism underlying its actions remains unclear. In this study, we evaluated the effects of maitotoxin (MTX) on the interaction of guanine nucleotides with G-protein {alpha} sub-units. Equilibrium binding of the nonhydrolyzable GTP analog, GTP{gamma}S, to {alpha} subunits (Go, Gs, Gil, Gi2, and Gi3) was decreased in the presence of MTX. Furthermore, reconstitution of G{alpha} with Gβ{gamma} dimer showed a reversal of the inhibition elicited by MTX. GDP/GTP exchange rate for G{alpha} subunits was significantly inhibited in the presence of MTX. MTX had no effect on the rate of GDP or GTP dissociation from {alpha} subunits. Also, the mastoparan-induced component of nucleotide exchange is not effected by MTX. These results suggest that MTX acts on G{alpha} subunits to modulate their interaction with guanine nucleotides, perhaps by stabilizing an empty state of the {alpha} subunit. Accordingly, MTX may disrupt the normal signal transduction pathways by inhibiting GTP binding to G{alpha} subunits and interfering with the GDP/GTP exchange.

Key Words: G{alpha} Subunit • G-Proteins • Maitotoxin • Marine Toxin

International Journal of Toxicology, Vol. 20, No. 1, 39-44 (2001)
DOI: 10.1080/109158101750103396
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