Endoplasmic Reticulum Structure and Function

Endoplasmic Reticulum (ER) Structure and Function

• The ER is a network of membrane-enclosed tubules and sacs (cisternae) that extends from the nuclear membrane throughout the cytoplasm.
• It's the largest organelle in most eukaryotic cells.
• The ER can comprise greater than 10% of the total cell volume.

Types of ER

• Rough ER (RER) or Granular ER (GER): Covered by ribosomes on its outer surface.
  • Involved in protein production, processing, folding, and quality control.
  • Not associated with ribosomes.
• Smooth ER (SER) or Agranular ER:
  • Tubular or vesicular in form.
  • Not involved in protein synthesis.
  • Functions in lipid metabolism in different cell types, including lipid synthesis, metabolism, muscle contraction, and detoxification.

SER Functions

• Lipid synthesis: Synthesizes phospholipids, cholesterol, and ceramide, the essential components of cell membranes.
• Steroid hormone biosynthesis: Synthesizes steroid hormones.
• Metabolism in liver cells: Metabolizes lipid-soluble compounds, harmful drugs, and alcohol, by converting them to water-soluble compounds for excretion in the urine.
• Muscle contraction: Participates in the contraction process in muscle cells as sarcoplasmic reticulum (SR).
• Lipid transport: Involved in lipid transport.

Phospholipids

• Phospholipids are a group of lipids that consist of two hydrophobic fatty acids, a hydrophilic glycerol unit, and a phosphate group which is esterified to an organic molecule (e.g., choline, ethanolamine, inositol).

Sphingolipids

• Ceramides are a family of waxy lipid molecules composed of sphingosine and a fatty acid.
• Ceramides are found in high concentrations within the cell membrane of eukaryotic cells.
• Component lipids of sphingomyelin, one of the major lipids in the lipid bilayer.

Cholesterol

• Cholesterol is a sterol (or modified steroid) lipid.
• More than 90% of cellular cholesterol is located at the plasma membrane.
• High cholesterol can lead to fatty deposits in blood vessels.

Smooth ER and Lipid Synthesis

• ER is the major site for synthesizing membrane lipids in eukaryotic cells.
• Membrane lipids are synthesized in association with already existing membranes (hydrophobic) rather than in the aqueous environment of the cytosol.
• Membrane lipids are then transported from the ER to their final destinations via vesicles or carrier proteins.

Smooth ER and Lipid Synthesis: Vesicles

• A vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer.

Smooth ER and Lipid Synthesis: Carrier Protein

• A carrier protein is a membrane protein that moves solutes across the membrane by creating conformational changes in the protein.

Smooth ER and Lipid Synthesis (Phospholipids): Chemical Process

• Most phospholipids are derived from glycerol.
• Synthesized on the cytosolic side of the ER membrane from water-soluble cytosolic precursors.
• Resulting phospholipid (e.g., phosphatidic acid) is inserted into the membrane.
• Enzymes on the cytosolic side of the ER membrane then modify phosphatidic acid or catalyze the addition of different polar head groups, including phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine, and phosphatidyl inositol.
• These are formed from phosphatidic acid via a modified diacylglycerol.

SER and Steroid Hormones

• SER contains the enzymes needed to synthesize steroid hormones, which are abundant in steroid-producing cells (e.g., Leydig's cells in testes, adrenal cortex cells, corpus luteum cells in ovaries).
• Steroid hormones are synthesized from cholesterol.

SR and Muscle Contraction

• SR (sarcoplasmic reticulum) is a smooth endoplasmic reticulum found within muscle cells.
• The main function of the SR is to store calcium ions (Ca2+).
• The SR specifically regulates Ca2+ ion flow; Ca2+ ions regulate muscular contraction.
• Ca2+ ions bind to the Troponin C component of the actin filament, exposing binding sites for the myosin head to bind to; this stimulates muscle contraction.
• SR membrane contains Ca2+-ATPase pumps.
• SR system consists of a branching network of SER cisternae surrounding each myofibril.

Types of Muscle

• Smooth muscle: Involuntarily contracts internal organs, blood vessels.
• Cardiac muscle: Involuntarily contracts in the heart.
• Skeletal muscle: Voluntarily contracts bones of the skeleton.

Muscle Structures

• Myocytes are muscle cells.
• Muscle tissue is composed of muscle fibers, which are bundles of tubular myofibrils.
• Myofibrils are composed of repeating sarcomeres.
• Sarcomeres are the functional units of a muscle fiber.
• Actin and myosin are two proteins found in all muscle tissue. Myosin (15nm) is a thick filament, and actin (7nm) is a thinner filament.
• Contraction is driven by the interaction of actin and myosin filaments.

Muscle Contractions

• Actin and myosin work together for muscle contraction and movement; a motor neuron releases acetylcholine into the muscle cell.
• Acetylcholine triggers the release of calcium ions from the sarcoplasmic reticulum.
• Calcium ions bind to troponin, changing its shape and moving tropomyosin away from the myosin-binding sites on actin.
• Myosin heads bind to actin, forming cross-bridges.
• Myosin pulls actin filaments towards the center of the sarcomere (ATP energy).
• The sarcomere shortens, causing the muscle fiber to contract.

SER and Liver Metabolic Reactions

• Abundant in the liver, SER contains specific enzymes that metabolize lipid-soluble compounds and inactivates harmful drugs (e.g., phenobarbital), converting them into water-soluble compounds that are eliminated via the urine.
• Also detoxifies alcohol and certain toxic compounds, certain hormones.
• Cytochrome P450 is a large family of enzymes in the SER of liver cells; plays a significant role in drug metabolism.

Glycogen Breakdown

• SER membranes contain Glucose-6-phosphatase in the liver.
• This enzyme is involved in breaking down glycogen into glucose.

ER in Protein Synthesis

• GER: Involved in protein synthesis and secretion.
  • Prominent in cells specialized for protein synthesis.
• Ribosomes: Attached to the GER's exterior.
  • Detected by light microscope by staining basic dyes
• Free ribosomes: Synthesize proteins destined to remain in the cytosol, nucleus, mitochondria, chloroplasts or peroxisomes.

Protein Synthesis in the GER(Detailed)

• All protein synthesis begins on free ribosomes in the cytosol, protein synthesis is resumed.
• Ribosomes synthesize secretory proteins and are subsequently targeted to the ER by a signal sequence (amino acid sequence) at the polypeptide chain's amino terminus.
• The signal sequence is about 16–20 amino acids long and appears at the beginning of the growing polypeptide chain.
• Signal peptides emerge; a special molecule (SRP; a protein-RNA complex) recognizes the sequence.
• SRP binds to the signal peptide and ribosome. Protein synthesis halts.
• SRP-ribosome complex attaches to the ER at specific sites (SRP receptors).
• SRP is released, and synthesis resumes.
• The growing polypeptide chain enters the translocon channel.
• The signal peptide is removed by signal peptidase.
• The polypeptide chain is released into the ER lumen.
• The ribosome detaches.
• Completed protein may be packaged into transport vesicles and move to Golgi. Further modifications may occur.

Post-translational Modifications

• Newly synthesized polypeptides in the ER undergo five modifications:
  1. Carbohydrate addition and processing
  2. Disulfide bond formation
  3. Specific proteolytic cleavages
  4. Protein folding
  5. Assembly into multimeric proteins

Protein Folding, Glycosylation

• ER is the site of protein folding, assembly, disulfide bond formation, and initial glycosylation steps (modification of proteins with carbohydrates).
• Luminal ER proteins' primary role is assisting newly translocated polypeptides' folding and assembly.
• Translocated proteins enter the ER as unfolded peptides.
• Chaperons (e.g., Bip/Hsp70) facilitate folding.
• Disulfide bond formation enhances protein stability.

Export from ER

• Correctly folded proteins are transported to the Golgi apparatus.
• A protein export system in ER transports proteins through vesicles from the ER exit sites (ERES) through ER-Golgi intermediate compartment (ERGIC).
• Incorrectly folded proteins are targeted for degradation.
• ER exports proteins and lipids in vesicles, which carry them to the Golgi apparatus.

Additional Information

• Details on video links provided at the end of the document.

This quiz covers the structure and functions of the Endoplasmic Reticulum (ER), focusing on its two types: Rough ER and Smooth ER. You'll explore the essential roles these organelles play in protein production and lipid metabolism. Test your knowledge on how the ER contributes to cellular functions and its significance in eukaryotic cells.