A FRET-based approach for quantitative evaluation of forskolin-induced pendrin trafficking at the plasma membrane in bronchial NCI H292 cells.

[pendred syndrome]

Human pendrin (SLC 26 A 4 , PDS ) is an integral membrane protein acting as an electroneutral anion exchanger . Loss of function mutations in pendrin protein cause Pendred syndrome , a disorder characterized by sensorineural deafness and a partial iodide organification defect that may lead to thyroid goiter . Additionally , pendrin up-regulation could play a role in the pathogenesis of several diseases including bronchial asthma and chronic obstructive pulmonary disease (COPD ). Therefore , monitoring the plasma membrane abundance and trafficking of pendrin in the context of a living cell is crucially important .Trafficking of pendrin to the plasma membrane was monitored by fluorescence resonance energy transfer (FRET ), a physical phenomenon occurring between two fluorophores (the FRET donor and acceptor ) located in close spatial proximity . Because the efficiency of the energy transfer is inversely proportional to the sixth power of the distance between donor and acceptor , FRET is extremely sensitive to small changes in distance between the donor and acceptor and is therefore a powerful tool to determine protein-protein interactions .FRET studies revealed that forskolin-induced cAMP production is associated with a significant increase of pendrin expression at plasma membrane , which is paralleled by a decrease in intracellular pH . Pendrin transposition to the membrane is accompanied with a partial depolymerization of actin cytoskeleton via Rho-GTPase inhibition .Trafficking to the plasma membrane is critical in the regulation of pendrin activity . Therefore , reliable tools for monitoring and quantifying this phenomenon are highly desirable .

Diseases
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Diseases presenting "a partial iodide organification defect that may lead to thyroid goiter" symptom

pendred syndrome

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