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Detection of Detergent-sensitive Interactions Between Membrane Proteins
Published on: March 7, 2018
La clonación funcional de TUG como regulador del transportador de glucosa GLUT4 que hace tráfico
Jonathan S Bogan1, Natalie Hendon, Adrienne E McKee
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. jonathan.bogan@yale.edu
Nature
|October 17, 2003
Resumen
Los investigadores identificaron TUG como una proteína que se une al transportador de glucosa tipo 4 (GLUT4) dentro de las células. La señalización de la insulina libera esta atadura, permitiendo que GLUT4 se mueva a la superficie celular para la captación de glucosa.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Fisiología Fisiología Fisiología.
Sus antecedentes:
- La insulina regula la absorción de glucosa moviendo el transportador GLUT4 a la superficie celular.
- Los mecanismos que controlan el secuestro intracelular de GLUT4 no se comprenden completamente.
Objetivo del estudio:
- Para identificar las proteínas involucradas en la regulación del tráfico intracelular de GLUT4.
- Aclarar el papel de TUG en el secuestro de GLUT4 y la movilización mediada por insulina.
Principales métodos:
- Cribado funcional para identificar las proteínas que modulan la distribución de GLUT4.
- Ensayos de inhibición dominantes-negativos utilizando TUG. truncado.
- Coinmunoprecipitación para evaluar la formación del complejo TUG-GLUT4.
- Microscopía de inmunofluorescencia para determinar la localización subcelular de TUG y GLUT4.
Principales resultados:
- TUG fue identificado como una proteína de unión a GLUT4 que contiene un dominio UBX.
- El TUG truncado inhibió la redistribución GLUT4 estimulada por insulina.
- TUG de longitud completa formó un complejo con GLUT4, que fue desmontado por la insulina.
- TUG endógeno localizado con GLUT4 intracelular en los adipocitos 3T3-L1.
Conclusiones:
- TUG actúa como un cable intracelular para GLUT4, atrapándolo dentro de la célula.
- La señalización de la insulina interrumpe la interacción TUG-GLUT4, liberando GLUT4 para el transporte en la superficie celular.
- TUG juega un papel crítico en la regulación de la homeostasis de la glucosa mediante el control del tráfico de GLUT4.
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