WI

Vesicular Transport and Membrane Fusion

Lesson Objectives

  • Explain how vesicles fuse with membranes.

  • Predict pathologies based on dysfunction of vesicular transport.

Review Refresher

  • Arrange the following events in order from beginning to end:

    1. Vesicle coat forms.

    2. Cargo proteins are localized together.

    3. GTP hydrolysis to free vesicle from donor.

    4. Vesicle coat releases.

Vesicle Docking and Fusing: Beam me up, RaB!

  • Rab-GTP binds to Rab effectors (tether) on target membrane.

  • V-SNARE (vesicle-SNARE) proteins on the vesicle interact with t-SNARE (target-SNARE) proteins on the target membrane, forming the SNARE complex.

  • Proximity of the vesicle and target membranes facilitates the fusing of the membranes, one leaflet at a time, spontaneously.

  • ATPases hydrolyze ATP to provide the energy to dissociate the SNARE complex.

  • Rab-GTP completes the “Rab cycle.” Reference to Figure 14-11 in Molecular and Cellular Biology (MCB).

Practice Problem

Imagine examining the cells of a dead body that has entered rigor mortis. At which stage of membrane fusion would you be most likely to observe the cells in?

  • Options:

    1. Before Rab and the Rab effector bind.

    2. Before the SNAREs have twisted but after Rab has docked.

    3. After the SNAREs have twisted but before they have been separated.

    4. After SNAREs have dissociated but before Rab has relocated.

Rab Cycle

  • GTPase Activating Protein (GAP) hydrolyzes Rab-GTP to Rab-GDP.

  • Rab-GDP is bound by Glutamine Dissociation Inhibitor (GDI) and shuttled back to donor membrane.

  • A Guanine Exchange Factor (GEF) in the donor membrane exchanges GDP for GTP. Reference to Nature Reviews Molecular Cell Biology (2025).

Drawing Exercise

  • With your SLG, draw as much of the formation and fusing of vesicles in the endocytotic-exocytotic cycle as you can remember.

Receptor and Protein Coat Recycling

  • Proteins are expensive to make, so cells avoid having to remake them. Reference to Nature Reviews Molecular Cell Biology (2025).

True or False Exercises

  • True or false: You are most likely to find COPS near the cis-Golgi complex.

  • Repeated statement for emphasis.

The Endosome: A Hub of Activity

  • Vesicles and vacuoles (endosomes more broadly) are essential for transporting, sorting, and storing a variety of materials used by cells.

  • Endosomes exhibit different surface proteins as they progress from budding to maturity and fusion with other organelles. Reference to Figure 14-31 in MCB.

More True or False Exercises

  • True or false: Signaling proteins in endosome membranes are added after the endosome is formed.

  • Repeated statement for emphasis.

Signs of Maturity in Endosomes

  • Most materials taken by the cell or produced by the cell end up in a lysosome.

  • Ubiquitin is a nearly universal signal for degradation.

  • Late-stage endosomes assemble ESCRT complexes with the help of Ubq-tagged Hrs proteins.

  • ESCRT proteins help form multivesicular bodies as targets for lysosomal activity. Reference to Figure 14-32 in MCB.

Practice Problem

Histamine is a chemical released by certain white blood cells in the body in response to trauma. Where are white blood cells likely to store histamine?

  • Options:

    1. Golgi complex

    2. Vesicles

    3. Nucleus

    4. ER

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's Disease

  • A key cellular feature of individuals with ALS is the fragmentation of the Golgi complex.

  • Prediction question: How does the abnormal form of the Golgi complex lead to loss of motor control?

Another Insight on ALS

  • Neurotransmitters, chemicals used to send signals from one neuron to another, are normally stored in vesicles near the axon terminal of neurons.

  • Golgi complex degradation reduces protein synthesis, which depletes the storage of neurotransmitters in the neuron.

  • The cause of ALS is still unknown. Reference to Casey Henley (2025).

Discussion Prompt

  • Discuss with your SLG: What would be the likely pathology of a disease in which the v-SNARE and t-SNARE proteins do not bind together optimally?

Lesson Objectives

  • Describe the purpose of binding proteins in trafficking vesicles.

  • Explain how vesicles fuse with membranes.

  • Predict pathologies based on dysfunction of vesicular transport.