Endomembrane System

Learning Objectives

  • Make a flow chart showing how proteins are processed and packaged or unpackaged as they move from ribosomes to the interior of the rough ER to Golgi to motor proteins to their destination.

  • Predict the effects on a particular protein or overall cell function if a specified element or process in the endomembrane system was altered.

Clicker: Warmup

Claim Evaluation

  • Statement: “While it is very rare, a species of bacteria could have a Golgi Apparatus.”
      - A. True: Some bacteria can contain membrane-bound organelles, though it is rare.
      - B. False: Bacteria never have eukaryotic organelles.
      - C. False: It is not rare for a bacterial cell to have a Golgi Apparatus.

Importance of the Endomembrane System

Tay-Sachs Disease

  • Characterized by abnormal accumulation of macromolecules inside the lysosome.

  • Genetic disease, no cure, primarily affects children, and is often fatal within months to years of birth.

  • Caused by a mutation in a single enzyme (Hexosaminidase A, HEXA) required for lipid and glycoprotein metabolism.

  • Leads to progressive deterioration of nerve cells.

Overview of the Endomembrane System

Components

  • Vesicle: Involved in the transportation of proteins and lipids.

  • Organelle Structures:
      - Smooth ER
      - Rough ER
      - Golgi Complex
      - Lysosomes
      - Nuclear Envelope

Function

  • Primary center for protein and lipid synthesis, modification, and transport.

How Proteins Move Through the Endomembrane System

  • Proteins move from outside the cell to the inside, being transported around or out of the cell.

Overview of the Secretory System

  • Protein Production: Proteins are produced in the rough ER.

  • Protein Modifications: Some proteins undergo modifications.

  • Transportation: Proteins travel directionally through the Golgi.

  • Proteins and Lipids Sorting: Proteins and lipids are sorted.

  • Transport Mechanism: Proteins travel in vesicles, walked down microtubules by motor proteins (e.g., kinesin).

  • Target Interaction: Vesicles interact with the intended location, typically the plasma membrane.

The Endoplasmic Reticulum (ER)

Structure

  • Extensive membrane-enclosed factory.

Parts of ER

Smooth ER

  • Functions: Ca²⁺ storage and release; maintains a strong gradient across the membrane.
      - Lumen of smooth ER: 1 mM Ca²⁺ vs. cytoplasm: 10^{-4} mM
      - Rapid release of Ca²⁺ in response to signals.

Rough ER

  • Site of protein production for:
      - Secreted proteins.
      - Membrane proteins.
      - Proteins destined for organelles.
      - Proteins requiring modifications.

  • Continuous with the smooth ER but different protein composition.

  • Lacks attached ribosomes, hence 'smooth'.

  • Involved in lipid synthesis (phospholipids and steroids).

Function of Rough ER

  • Closer to the nucleus.

  • Over hundreds to thousands of ribosomes attached.

Clicker: Reasoning

  • Question regarding the impact of non-functioning smooth ER on the cell cycle.
      - A. Yes: Mitosis can occur without the smooth ER.
      - B. No: Some proteins required by the cell won't be synthesized.
      - C. No: New plasma membranes cannot be produced.
      - D. Yes: Rough ER can compensate for the smooth ER's loss.

How are Proteins Made in the Cell?

Translation

  • The process of creating proteins in a cell; part of the Central Dogma.

Ribosome Differences

Bound vs. Free Ribosomes

Bound Ribosomes Make:

  • Secreted proteins.

  • Membrane proteins.

  • Proteins destined for specified organelles.

  • Proteins needing specific modifications.

Free Ribosomes Make:

  • Proteins that function in the cytoplasm, some in the nucleus and mitochondria.

Endomembrane System Functions

  • Functions as an address tag or zip code.

  • Acts as a transport/delivery system that requires energy for regulation.

How Proteins Get Where They Need to Go

Sorting Mechanism

  • Proteins have specific codes for their location in the cell.

  • Example: Acid hydrolases shipped to lysosomes.
      - Signal Sequence: Directs proteins to the ER for translation.
      - Targeting Sequence: Directs completed proteins to specific cell locations.

Signal Sequence

Overview

  • Special signal sequence of ~20 hydrophobic amino acids directs proteins into the ER after translation starts.

  • Types of proteins:
      - Secretory proteins.
      - Integral membrane proteins (receptors, etc.).
      - Proteins for organelles like lysosomes.

Translocation into the Rough ER

Steps

  1. Translation begins in the cytoplasm, with the signal sequence binding to an RNA-protein particle.

  2. This particle moves the ribosome over to the ER where it binds to a receptor near a channel.

  3. Ribosome continues translating, and the protein enters the ER as it is being made (translocation).

Post-translational Processing

  • Upon reaching the ER, signal peptides for secreted proteins are removed after translocation is complete.

Impact of Removing Signal Sequence

Predictive Outcomes

  1. Protein made but lacking some amino acids.

  2. Protein not made by the ribosome.

  3. Protein made, remaining in the ER.

  4. Protein made in the cytoplasm, remaining there.

Targeting Sequences

Function

  • Ensure proteins reach the correct cellular location.

  • Distinct sequences include:
      - KDEL or KKXX for ER retention (C-terminal).
      - Nuclear localization sequence for nucleus targets (internal sequence).
      - Integral membrane proteins with ~20 hydrophobic amino acids.

Targeting Sequences Complexity

  • Targeting signals can appear throughout the peptide and vary by end location.

  • Proteins can possess both signal and targeting sequences or just one type.

Integral Membrane Proteins Insertion

Single-Pass Integral Membrane Proteins

  • A stop-transfer sequence prevents translocation inside and embeds the protein into the membrane.

Multi-Pass Integral Membrane Proteins

  • Feature multiple hydrophobic amino acid stretches, creating multiple membrane-spanning regions for their function.

  • Orientation is defined by charge and position of the sequences.

Clicker: Organelles Evaluation

  • Assessing the function of membrane proteins that rely on signal and stop-transfer sequences.

Secretory Pathway Overview

  • Proteins are synthesized in the rough ER, modified, sorted, and then transported through the Golgi and to their destinations via vesicles.