Video Experimental Relacionado
Updated: Jun 20, 2026
13:40
Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
Published on: July 7, 2011
La liberación regulada por esteroles de SREBP-2 de las membranas celulares requiere dos escisiones secuenciales, una
J Sakai1, E A Duncan, R B Rawson
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Cell
|June 28, 1996
Resumen
Las proteínas de unión a los elementos reguladores de esteroles (SREBPs) se liberan del retículo endoplasmático a través de dos hendiduras. Este proceso activa los genes para la síntesis y absorción del colesterol.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las proteínas de unión al elemento regulador de esteroles (SREBPs) son factores de transcripción clave que regulan la homeostasis del colesterol.
- Los SREBP se sintetizan como precursores anclados a la membrana del retículo endoplasmático a través de dominios transmembrana.
Objetivo del estudio:
- Para dilucidar el mecanismo de liberación de SREBP-2 de la membrana del retículo endoplasmático.
- Para identificar los sitios de escisión y los factores regulatorios involucrados en la activación de SREBP.
Principales métodos:
- Utilizó proteínas de fusión H-Ras-SREBP-2 para estudiar el procesamiento de SREBP.
- Se investigó la regulación del esterol y los eventos de escisión secuencial en el SREBP. ligado a la membrana.
Principales resultados:
- SREBP-2 se somete a dos escisiones proteolíticas secuenciales para su liberación de la membrana.
- La primera escisión es dependiente del esterol y ocurre en el bucle luminal; la segunda es independiente del esterol y ocurre dentro del primer dominio transmembrana.
- Las células del ovario del hámster chino mutante defectuosas en la segunda escisión son colesterol auxotrófico debido a la falla en la activación de SREBP.
Conclusiones:
- El mecanismo de escisión secuencial es esencial para activar la transcripción mediada por SREBP de los genes del metabolismo del colesterol.
- Comprender el procesamiento de SREBP proporciona información sobre la regulación del colesterol celular y los posibles objetivos terapéuticos.
Videos de Conceptos Relacionados
01:45Regulation of Nuclear Protein Sorting
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...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
01:26Insertion of Single-pass Transmembrane Proteins in the RER
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
01:29Insertion of Multi-pass Transmembrane Proteins in the RER
The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
01:27Post-translational Translocation of Proteins to the RER
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...
01:28Assembly of the Lipid Bilayer in the ER
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...