CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Na+/I- symporter plasma membrane expression relies on a carboxy-terminal PDZ-binding motif
Autor/es:
MARTIN, M; BERNAL BARQUERO, CE; PEYRET, V; NICOLA, JP; GEYSELS, RC
Lugar:
Buenos Aires
Reunión:
Congreso; XVII Latin American Thyroid Society Congress; 2019
Institución organizadora:
Latin American Thyroid Society
Resumen:
Na+/I-symporter (NIS)-mediated radioiodide accumulation constitutes the molecular basisfor the treatment of differentiated thyroid cancer. However, thyroid tumorsoften exhibit reduced I− transport as a consequence of abnormalitiesin the transport of the protein to the plasma membrane. Toinvestigate the role of the PDZ binding-motif TNL643 located at thecarboxy-terminal edge of the protein in NIS plasma membrane expression underphysiological conditions.Functionalin vitro studies were performed on non-polarizedor polarized MDCK-II epithelial cells stably expressing wild-type or PDZ-binding domain mutant NIS.Functionalstudies revealed that deletion of the PDZ-binding motif reduces I-uptake in non-polarized MDCK-II cells, because Δ640-643 NIS expression at theplasma membrane is significantly reduced. On Western blots, the fullyglycosylated NIS polypeptide was detected in Δ640-643 NIS-expressing cells,indicating that this mutant is retained beyond the medial-Golgi, where newlysynthesized membrane proteins are sorted to different subcellular compartments.Moreover, under polarized conditions, confocal microscopy revealed that Δ640-643NIS expression at the basolateral plasma membrane is significantly reduced dueto its intracellular retention in uncharacterized vesicles. Althoughthe molecular mechanisms that determine NIS plasma membrane expression inthyroid cells remain elusive, here, we provide evidence that thecarboxy-terminus edge of the protein contains a PDZ-binding motif involved inplasma membrane expression. The identification of PDZ-domain-containingNIS-interacting proteins may novel therapeutic interventions to increase theeffectiveness of radioiodide therapy.