Endoplasmic Reticulum

Endoplasmic Reticulum (ER)

A multifunctional organelle involved in synthesizing, folding, and processing proteins, as well as lipid synthesis.

Types of Proteins Synthesized in the ER

Includes proteins for the ER itself, Golgi apparatus, plasma membrane, and proteins destined for lysosomes and endosomes.

Protein Recognition for ER Translocation

Proteins are recognized by specific N-terminal hydrophobic signal sequences essential for their entry into the ER.

Signal Sequences in Protein Targeting

Hydrophobic sequences that inform the cellular machinery to guide proteins to the ER, often cleaved or retained during entry.

Role of Signal Recognition Particle (SRP)

SRP pauses translation of nascent proteins, preventing premature folding, and directs them to the ER for proper assembly.

SRP and Ribosome Delivery to the ER

After binding, SRP guides the ribosome-nascent protein complex to the ER membrane to enable translocation.

Binding Interactions of SRP

SRP binds the ER membrane's SRP receptor, facilitating the ribosome's attachment to the SEC61 translocon for protein entry.

SEC61 Translocon Function

Forms an aqueous channel to continue translation, allowing nascent polypeptides to enter the ER.

BiP Chaperone Function

Assists polypeptides entering the ER and aids in the proper folding of proteins lacking glycosylation.

Key Modifications in the ER

Includes formation of disulfide bonds and N-glycosylation, which are critical for protein stability and functionality.

N-Glycosylation Process

Involves adding an oligosaccharide chain to asparagine residues during translocation, crucial for protein stability.

Folding Monitoring Mechanism in the ER

N-linked oligosaccharides are trimmed to ensure proper folding, involving chaperones like Calnexin and ERp57.

Chaperone Role in Preventing Aggregation

Chaperones prevent the clumping of unfolded proteins, safeguarding cellular function and protein integrity.

ER-Associated Degradation (ERAD) Pathway

Targets misfolded proteins for degradation to prevent cellular dysfunction; involves mannose trimming for ubiquitination.

Cystic Fibrosis (CF) Overview

A genetic disorder caused by CFTR gene mutations affecting chloride transport, leading to thick mucus buildup in organs.

Symptoms and Complications of Cystic Fibrosis

Includes severe respiratory issues, heightened infection risk, and potential necessity for lung transplants.

CFTR Channel Role

Regulates chloride ion transport, essential for mucus hydration and viscosity in epithelial tissues.

CFTR F508 Mutation Impact

Leads to misfolded CFTR protein degradation before reaching the surface, disrupting chloride transport.

Treatment Approach for F508 Mutation

Lumacaftor stabilizes CFTR, improving chloride transport and lung function in CF patients.

Human Cytomegalovirus (HCMV) Immune Evasion

Utilizes the ERAD pathway to evade immune detection by inducing degradation of MHC class I molecules.

Cholera Toxin Effect on Intestinal Cells

Stimulates excessive chloride and water secretion in the intestines, causing severe diarrhea; facilitated by its B subunit binding to gut receptors.