ch. 15 cont.

• Peroxisomes


  Organelles that produce enzymes that breakdown toxins, alcohols and fatty acids, and synthesize certain phospholipids
• Peroxisomes


  • Produce enzymes that produce hydrogen peroxide
  • Bulk of proteins come from the cytosol
  • Some proteins arrive via vesicles that bud from the ER
• Import signal


  SKL (ser-lys-leu)
• Peroxisomal membrane


  Contains protein translocator

  
• Proteins do not need to unfold when entering the peroxisomes

  
• Zellweger syndrome


  Mutations that block peroxisomal protein import, affects liver, kidney, brain, affected individuals usually do not survive 6 months
• Protein sorting


  • Proteins enter peroxisomes from both the cytosol and the endoplasmic reticulum
  • Bulk of proteins come from the cytosol
  • Signal sequences, protein receptors and protein translocators are required for protein transport from cytosol to organelles such as the peroxisomes
  • Protein does not need to unfold to enter the peroxisome via translocator

  
• Mechanisms for proteins to be transported into organelles

  • Nuclear Pores
  • Protein Translocators
  • Transport Vesicles

  
• The endoplasmic reticulum is the most extensive membrane network in eukaryotic cells

  
• Proteins transported to the Golgi apparatus, endosomes, lysosomes, and the cell surface, first enter the ER from the cytosol

  
• Protein trafficking


  The process of moving proteins from the rough ER, through the Golgi apparatus, where they are modified and packaged into vesicles

  
• Proteins transported to the Golgi apparatus, endosomes, lysosomes, and the cell surface, all must first enter the ER from the cytosol

  
• A common pool of ribosomes synthesizes all the proteins encoded by the nuclear genome

  
• Proteins entering the ER


  • Water-soluble proteins cross the ER membrane completely and are released into the lumen
  • Soluble proteins made in the ER are released into the ER lumen
  • Transmembrane proteins only partially cross the ER and become embedded in the membrane
  • All these proteins are directed to the ER by a signal sequence of small hydrophobic amino acids

  
• KDEL


  1. terminal signal sequence for ER retention

  
• Protein entry into the ER


  • Signal peptide
  • SRP
  • SRP receptor
  • Translocator proteins
  • Start signal
  • Stop signals

  
• The signal sequence is guided to the ER membrane with a signal-recognition particle (or SRP) which binds the ER signal sequence in the new protein as it emerges from the ribosome

  
• In addition to directing proteins to the ER, the signal sequence functions to open the translocation channel

  
• Transmembrane protein arrangement in the lipid bilayer

  • Single-pass transmembrane protein is retained in the lipid bilayer
  • Double-pass transmembrane protein has an internal ER signal sequence

  
• Proteins are transported into organelles by three mechanisms: nuclear pores, protein translocators, and transport vesicles
• Signal sequences direct proteins to the correct compartment

  
• Proteins enter the nucleus through nuclear pores
• Proteins unfold to enter mitochondria and chloroplasts

  
• Proteins enter peroxisomes from both the cytosol and the endoplasmic reticulum

  
• Soluble proteins made on the ER are released into the ER lumen
• Start and stop signals determine the arrangement of a transmembrane protein in the lipid bilayer

  
• Sorting signal or signal sequence

  Example: hydrophobic signal sequence, KDEL

  
• Vesicular transport


  • Allows materials to exit or enter the cell
  • Exocytosis: a vesicle fuses with the plasma membrane, releasing its content to the cell's surroundings
  • Endocytosis: extracellular materials are captured by vesicles that bud inward from the plasma membrane
• For some proteins delivered to the ER, this is just their first "stop"; they are still destined for another location

  
• Transport vesicles


  • Carry soluble proteins and membrane between compartments
  • Bud from one membrane and fuse with another, carrying membrane components and soluble proteins between compartments of the endomembrane system and the plasma membrane
• Vesicle budding


  • Driven by the assembly of a protein coat
  • Vesicles coated on the cytosolic side
  • Examples: clathrin-coated vesicles, COP (coat protein)-coated vesicles
• Cargo receptor


  Receives a specific molecule to be delivered
• Adaptin


  Recognizes a specific cargo receptor
• Clathrin coat


  Shapes the membrane into a vesicle
• Dynamin


  Together with other proteins causes pinching off of the vesicle
• Types of coated vesicles

  • Clathrin-coated (clathrin + adaptin 1, Golgi apparatus, lysosome (via endosomes))
  • Clathrin-coated (clathrin + adaptin 2, plasma membrane, endosomes)
  • COPII-coated (COPII proteins, ER, Golgi cisterna)
  • COPI-coated (COPI proteins, Golgi cisterna, ER)
• Vesicle docking


  • Depends on Tethers and SNAREs
  • Rab proteins, tethering proteins, and SNAREs help direct transport vesicles to their target membranes
• SNARE proteins


  Aid in docking vesicles as well as catalyzing the membrane fusion process
• Molecules travel through a fixed sequence of membrane-enclosed compartments
• Vesicle docking


  Depends on tethers and SNAREs