JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us
Esta página ha sido traducida por una máquina. Otras páginas pueden seguir apareciendo en inglés. View in English

PGRMC2 es un chaperón hemo intracelular crítico para la función de los adipocitos

  • 0Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Nature +

|

22 de noviembre de 2019

|

22 de noviembre de 2019

Ver abstracta en PubMed

Resumen

Este resumen es generado por máquina.

El componente 2 de la membrana del receptor de progesterona (PGRMC2) transporta la señal del hemo dentro de las células. Esta proteína es crucial para la salud metabólica, y su modulación puede revertir los problemas relacionados con la obesidad.

Área De La Ciencia

  • Biología celular
  • Salud metabólica
  • La bioquímica

Sus Antecedentes

  • El hemo es vital para la función de las proteínas y la señalización celular.
  • Las vías de transporte intracelular para el hemo no se comprenden completamente.
  • Las mitocondrias sintetizan el hemo, pero su entrega a los objetivos celulares está mal definida.

Objetivo Del Estudio

  • Investigar el papel del componente 2 de la membrana del receptor de progesterona (PGRMC2) en el transporte intracelular del hemo.
  • Para aclarar la función de PGRMC2 en el tejido adiposo y su impacto en los procesos metabólicos.

Principales Métodos

  • Se investigó la función de PGRMC2 en el tejido adiposo marrón utilizando ratones knockout.
  • Se evaluaron los niveles de hemo nuclear lábil, la estabilidad de los represores transcripcionales sensibles al hemo (Rev-Erbα y BACH1) y la expresión génica.
  • Utilizó un activador PGRMC2 de molécula pequeña en ratones obesos y diabéticos.

Principales Resultados

  • La deleción de PGRMC2 en la grasa marrón redujo el hemo nuclear lábil y aumentó la estabilidad de Rev-Erbα y BACH1.
  • La deficiencia de PGRMC2 condujo a defectos mitocondriales, alteración de la termogénesis adaptativa y deterioro metabólico exacerbado en una dieta alta en grasas.
  • El tratamiento con activador de PGRMC2 mejoró las características diabéticas en ratones obesos.

Conclusiones

  • PGRMC2 es esencial para el transporte de hemo intracelular, particularmente hacia el núcleo.
  • La dinámica del hemo del tejido adiposo, mediada por PGRMC2, influye significativamente en la fisiología sistémica.
  • La modulación de PGRMC2 presenta una estrategia terapéutica potencial para los trastornos metabólicos relacionados con la obesidad.

Videos de Conceptos Relacionados

GPCRs Regulate Adenylyl Cylase Activity 01:09

7.1K

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...

Regulation of the Unfolded Protein Response 01:31

2.9K

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Export of Misfolded Proteins out of the ER 01:32

4.9K

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

The Unfolded Protein Response 01:37

6.1K

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

GPI Anchoring of Proteins in the ER Membrane 01:29

5.2K

GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...

Protein Modifications in the RER 01:26

6.7K

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...