Ch 7 The Endomembrane System

The Endomembrane System and Protein Trafficking in Eukaryotic Cells
Initial Protein Synthesis and General Targeting Principles

  • Universal Start: All proteins begin synthesis on cytosolic ribosomes.

  • ER Signal Sequence: Proteins destined for the endomembrane system have an ER signal sequence, directing ribosomes to the Rough ER (RER).

  • Cytoplasmic Proteins: Proteins lacking an ER signal sequence complete synthesis on free ribosomes and function in the cytoplasm.

  • Other Organelle Targeting: Proteins for non-endomembrane organelles (e.g., nucleus, mitochondria) are synthesized in the cytoplasm with specific targeting sequences.

Components of the Endomembrane System

  • Key organelles: Endoplasmic Reticulum (ER) (mainly RER), Golgi Apparatus, Plasma Membrane, Lysosome.

  • Vesicles: Facilitate transport and trafficking between components.

Classes of Proteins Entering the Endomembrane System

  • Secretory Proteins: Released by the cell into the extracellular environment.

  • Integral Membrane Proteins: Embedded in membranes of the plasma membrane or endomembrane organelles. Synthesized on RER.

The Secretory Pathway: ER to Extracellular Environment

  1. Entry into ER: Proteins enter the ER lumen; initial processing occurs.

  2. Vesicle Budding from ER: Proteins packaged into vesicles from the ER.

  3. Transport to Golgi: Vesicles fuse with the Golgi apparatus.

  4. Golgi Processing and Sorting: Proteins undergo further modification and are sorted for various destinations.

  5. Exit from Golgi: Proteins exit the trans Golgi network in vesicles.

  6. Fusion with Plasma Membrane: Vesicles fuse with the plasma membrane.

    • Secretory proteins are released outside the cell.

    • Integral membrane proteins become embedded in the plasma membrane.

  • Sequence: ER →\to Golgi →\to Plasma Membrane →\to Outside of Cell (for secreted proteins).

Lumen Equivalence and Integral Membrane Protein Orientation

  • Orientation: Cytoplasmic parts of integral membrane proteins remain cytoplasmic; lumenal parts become extracellular.

  • Lumen Equivalence: ER and Golgi lumen are topologically equivalent to the outside of the cell.

Golgi-Mediated Protein Sorting to Other Destinations

  • To Lysosomes: Golgi sorts specific proteins into vesicles for transport to lysosomes.

  • ER Retention/Retrieval: Golgi also sorts and returns ER-resident proteins back to the ER.

Endocytosis and Phagocytosis: Entry into the Endomembrane System

  • Endocytosis: Cells take in external materials via endocytic vesicles.

    • Pathway: Endocytic vesicle →\to Early Endosome →\to Late Endosome.

    • Materials can go to lysosomes; receptors are often recycled back to the plasma membrane via the trans Golgi.

  • Phagocytosis: Ingestion of large particles forming a phagosome.

    • Pathway: Phagosome →\to Lysosome for degradation.

  • Autophagy: Damaged intracellular structures are sent to lysosomes for degradation.

Summary of Traffic within the Endomembrane System

  • Protein synthesis starts in cytosol; ER signal sequence directs to Rough ER.

  • ER: Initial processing.

  • Vesicles: Transport between compartments.

  • Golgi: Central processing and sorting hub for secretion, plasma membrane, lysosomes, or ER return.

  • Endocytosis/Phagocytosis: Bring external materials into the system, often for lysosomal degradation, with receptor recycling.

  • Autophagy targets internal cellular components for lysosomal breakdown.