Copy of Chapter 13 Part 1 A (first half) lectures 1-4.pptx

BIO 344 - Cell and Molecular Biology

Molecular Biology of the Cell - Chapter 13: Intracellular Membrane Traffic

Key Pathways

  • Biosynthetic Secretory Pathway

    • Exocytosis: Delivery of synthesized proteins, carbohydrates, and lipids to the plasma membrane or extracellular space.

    • Process of Exocytosis:

      1. Molecules modified in the endoplasmic reticulum (ER).

      2. Storage until needed and delivery to the plasma membrane.

  • Endocytosis

    • Removal of plasma membrane components and transport to internal compartments (endosomes) for recycling or degradation.

    • Process of Endocytosis:

      1. Uptake of large molecules (e.g., vitamins, lipids).

      2. Sorting in endosomes for recycling or degradation in lysosomes.

Intracellular Vesicular Transport

  • Definition: Connects topologically equivalent compartments using vesicular transport and membrane fusion.

  • Compartments Involved:

    • Cytosol, Nucleus, Plastids, Peroxisomes, Mitochondria, Endoplasmic Reticulum, Golgi apparatus, Secretory vesicles, Early and Late Endosomes, Lysosomes.

  • Types of Transport:

    • Gated transport, transmembrane transport, and vesicular transport.

  • Topology: Lumen of each compartment is topologically equivalent to the cell exterior, allowing protein transfer without cross-membrane transit.

Vesicular Transport Mechanisms

  • Vesicular transport requires selectivity to ensure correct cargo is delivered to appropriate compartments.

  • Coated Vesicles:

    • Types:

      • Clathrin: Used for transport from Golgi to lysosomes and from plasma membrane to endosomes.

      • COPI and COPII: Involved in transport from Golgi to ER and vice versa.

  • Coat Protein Functions:

    1. Mold the vesicle during formation.

    2. Select the cargo to be transported.

    3. Disassemble (uncoat) for fusion with target membranes.

Clathrin-Coated Vesicles

  • Structure: Comprises heavy and light chains forming a triskelion structure, which assembles into a basket-like framework.

  • Assembly Process:

    • Adaptins attach to the membrane, binding specific cargo receptors and shaping the vesicle.

    • Cargo receptors select cargo based on membrane identity.

Phosphoinositides and Adaptin Recruitment

  • Phosphoinositides (PIPs):

    • Includes PI, PI(4)P, PI(4,5)P2, PI(3,4,5)P3, marking membrane regions and creating binding sites for proteins.

  • Adaptor proteins (AP2):

    • Recruit adaptins to membrane and bind to cargo receptors and clathrin for vesicle formation.

    • Complex interactions establish the identity of the vesicle and ensure correct cargo selection.

GTPases in Coat Recruitment

  • Monomeric GTPases: Control coat assembly at specific membrane locations.

  • Key Roles:

    • GTP-bound state is active; GDP-bound is inactive.

    • Regulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs).

  • COPII and COPI Formation:

    • Sar1: Acts as coat recruitment GTPase to initiate COPII vesicle formation at the ER.

Summary of Vesicle Formation Steps

  1. Formation: Coat proteins (e.g., clathrin, COPII) assemble on specific membranes.

  2. Pinching Off: Dynamin forms a ring to intiate membrane fusion and vesicle release from the donor membrane.

  3. Uncoating: The coat proteins disassemble to allow vesicle fusion with target membranes.

Conclusion

  • The intricate processes of vesicular transport, from biosynthetic pathways to endocytosis, ensure that cellular compartments maintain their identities and functionalities while effectively communicating and exchanging cargo. Understanding these processes is essential for grasping cell function and molecular interactions.