Video Experimental Relacionado
Updated: Apr 14, 2026
08:59
4D Imaging of Protein Aggregation in Live Cells
Published on: April 5, 2013
17.9K
Las proteínas PolyQ interfieren con la degradación nuclear de las proteínas citosólicas mediante el secuestro de la
Sae-Hun Park1, Yury Kukushkin, Rajat Gupta
1Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
Cell
|June 25, 2013
Resumen
Los agregados de expansión de poliglutamina (polyQ) secuestran la chaperona Sis1p, bloqueando el aclaramiento de la proteína. La restauración de los niveles de Sis1p restablece la degradación de las proteínas y la importación nuclear para la descomposición proteasomal.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La neurociencia es la neurociencia.
Sus antecedentes:
- El control de la calidad de las proteínas es crucial para prevenir enfermedades neurodegenerativas relacionadas con la agregación de proteínas.
- El sistema ubiquitina-proteasoma (UPS) elimina las proteínas mal plegadas, pero su función puede verse afectada en los estados de enfermedad.
Objetivo del estudio:
- Investigar cómo la agregación de poliglutamina (polyQ) interrumpe el aclaramiento de proteínas mal plegadas por el UPS.
- Identificar los mecanismos específicos por los cuales la expansión de polyQ interfiere con las vías de control de calidad de las proteínas celulares.
Principales métodos:
- Utilizó un modelo de levadura que expresaba proteínas poliQ-expandidas y un reporter de proteína mal plegada (CG() -GFP).
- Se empleó un análisis proteómico cuantitativo para identificar las proteínas secuestradas.
- Investigó el papel de la chaperona Hsp40 Sis1p y su homólogo en mamíferos DnaJB1.1.
Principales resultados:
- La expansión de PolyQ inhibió la degradación mediada por UPS de CG() -GFP sin afectar la ubicuidad o la actividad del proteasoma.
- Los agregados de PolyQ secuestraron la esencial chaperona Hsp40 Sis1p, un factor que limita la velocidad para el despeje.
- La sobreexpresión de Sis1p rescató la degradación CG() -GFP.
- Sis1p/DnaJB1 media la entrega nuclear de proteínas mal plegadas para la degradación proteasoma, y la agregación poliQ impide esta importación nuclear.
Conclusiones:
- La agregación de PolyQ perjudica el control de la calidad de las proteínas al secuestrar el chaperón Sis1p.
- Sis1p actúa como un mediador crucial para la entrega de proteínas mal plegadas al núcleo para la degradación de UPS.
- Los niveles de Sis1p son críticos para mantener la eficiencia de esta vía de control de calidad de proteínas nucleo-citoplasmáticas.
Videos de Conceptos Relacionados
02:18The Proteasome
10.7K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.7K
01:45Regulation of Nuclear Protein Sorting
3.5K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.5K
01:27Post-translational Translocation of Proteins to the RER
8.2K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
8.2K
01:32Export of Misfolded Proteins out of the ER
5.7K
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...
5.7K
01:13The Proteasome
2.0K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
2.0K
01:26Bacterial Protein Maturation
720
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
720