Biomedical Sciences I - Endomembrane System

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Biomedical Sciences I - Cellular Biology I

• Course instructor: Lorena Di Pietro
• Instructor email: [email protected]

The Endomembrane System

• Present in all eukaryotic cells
• Consists of distinct compartments bounded by membranes
• Forms an extensive network of interconnected tubules and flattened sacs

Endomembrane System - Components

• Rough endoplasmic reticulum (RER)
• Smooth endoplasmic reticulum (SER)
• Golgi apparatus
• Lysosomes
• Endosomes

The Endomembrane System - Function

• The organelles are part of a dynamic network.
• Materials are shuttled back and forth between the different compartments.
• Transport vesicles move materials between organelles in a directed manner.
• Motor proteins and cytoskeletal elements are key to transport vesicle movement.

Endomembrane System - Pathways

• Biosynthetic pathway: proteins are synthesized in the ER, modified in the Golgi, and transported to various destinations.
• Example destinations include membrane proteins, and lysosomal enzymes.
• Secretory pathway: proteins destined to be secreted from the cell (e.g., extracellular matrix proteins, hormones, neurotransmitters).
• Endocytic pathway: materials move from the cell surface to the intracellular space

The Endoplasmic Reticulum (ER)

• The widest subcellular structure in eukaryotic cells
• Network of membranous tubules and sacs called cisternae.
• Contains an extensive lumen that is separated from the cytosol by the ER membrane
• The outer nuclear membrane is continuous with the ER membrane; therefore, the perinuclear cavity is also continuous with the ER lumen.
• The ER is a dynamic structure with a changeable shape and size.

Rough Endoplasmic Reticulum (RER)

• Continuous with the outer nuclear membrane
• Ribosomes are attached to the cytoplasmic surface of the membrane.
• Under electron microscope it appears as rough.

Rough Endoplasmic Reticulum (RER) - Functions

• Synthesis of proteins
• Protein folding
• Initiation of glycosylation
• Quality control of proteins

Protein Synthesis

• Proteins destined for cytosol, nucleus, mitochondria, peroxisomes are made by free ribosomes in the cytosol.
• Proteins destined for ER, Golgi, lysosomes, plasma membranes, or secretion are made by bound ribosomes attached to the RER and move into the ER for further modifications

Protein Maturation

• Proteins are addressed to their correct location by specialized sorting signals.
• Sorting signals are encoded within the amino acid sequence.
• Sorting signals are recognized by specific receptors on the cellular membranes.
• Signal sequences are often removed after the protein has been sorted.
• There are 3 different ways proteins move between compartments: gated transport, protein translocation, and vesicular transport.

Rough Endoplasmic Reticulum - functions

• One-third of the mammals' proteins are synthesized on ribosomes attached to the RER.
• Proteins enter RER lumen and are translocated through, where they are either secreted or become integral membrane proteins.
• These proteins are further modified in RER lumen.

Rough Endoplasmic Reticulum - functions (continued)

• Synthesis of secreted proteins
• Integral membrane proteins
• Soluble proteins
• Glycosylation
• Protein folding
• Quality control

Rough Endoplasmic Reticulum - Protein Folding and Quality Control

• Newly synthesized proteins are screened by a quality control system composed of molecular chaperones.
• These components determine if the protein is properly folded and ready to move to the next cellular compartment.
• Misfolded proteins are recognized, moved to the cytosol, and degraded

Congenital Diseases of Glycosylation

• Inherited metabolic disorders that impact organ systems.
• These disorders arise when crucial enzymes for glycosylation are missing or dysfunctional.
• Mutations impede the glycosylation pathways in the ER.
• Cystic fibrosis is caused by mutations in the CFTR gene.
• This gene encodes a plasma membrane protein and transport channel, responsible for chloride regulation.
• The ER's quality control system often degrades mutant CFTR proteins, even if they might function effectively elsewhere.

Smooth Endoplasmic Reticulum (SER)

• Lacks ribosomes
• Usually smaller than RER
• Located farther from the nucleus
• Tubular cavities in continuous with RER

Smooth Endoplasmic Reticulum (SER) - Functions

• Sequestering calcium ions within the cytoplasm of cells.
• Synthesis of steroid hormones in endocrine cells (gonads and adrenal cortex).
• Detoxification of drugs and harmful compounds in liver cells.
• Principal site of production of lipoprotein particles in liver cells.
• Synthesis of phospholipids and cholesterol.

Golgi Complex

• Stack of flattened cisternae with thickened borders.
• Associated tubules and vesicles.
• Contains from a few to several thousands per cell.
• It's a polarized organelle with distinct faces.
• The cis face is closer to the ER and receives vesicles.
• The trans face is opposite to the cis face and releases vesicles.

Golgi Complex - Functions

• Handling/packaging center of the cell
• Modification and synthesis of carbohydrate portions of glycoproteins.
• Synthesis of glycolipids and sphingomyelin
• Lipid metabolism (e.g., sphingomyelin synthesis from ceramide).
• Glycosylation of proteins

Golgi Complex - Functions (continued)

• Glycosylation of lysosomal proteins (e.g., addition of mannose-6-phosphate).
• Modification of N-linked oligosaccharides.
• Sorting and transport, e.g., proteins to lysosomes.