17.2 Vesicle formation, targeting, and fusion

Vesicle formation and transport are crucial for cell function. Coat proteins like clathrin and COP complexes shape vesicles and select cargo, while adaptor proteins ensure specific molecules are packaged. This process is essential for moving materials between cellular compartments.

Vesicles bud from donor membranes, travel to target locations, and fuse to deliver their contents. Key players in this process include SNARE proteins, Rab GTPases, and tethering factors. These mechanisms enable vital functions like neurotransmitter release and hormone secretion.

Vesicle Formation and Cargo Selection

Role of coat proteins

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• Coat proteins play a crucial role in vesicle formation and cargo selection
  • Clathrin coat proteins form clathrin-coated vesicles involved in endocytosis and transport from the trans-Golgi network to endosomes
  • COPII coat proteins facilitate anterograde transport from the endoplasmic reticulum (ER) to the Golgi apparatus
  • COPI coat proteins mediate retrograde transport from the Golgi apparatus to the ER and within the Golgi cisternae
• Coat proteins interact with cargo adaptor proteins to selectively package specific cargo molecules (receptors, enzymes) into vesicles
  • Adaptor proteins recognize and bind to specific cargo molecules
  • Adaptor proteins also interact with coat proteins to facilitate cargo packaging into forming vesicles

Vesicle Budding, Targeting, and Fusion

Mechanisms of vesicle transport

• Vesicle budding
  1. Coat proteins assemble on the donor membrane and induce membrane curvature
  2. Cargo molecules are selectively incorporated into the forming vesicle through interactions with adaptor proteins
  3. Vesicle scission occurs, releasing the vesicle from the donor membrane
• Vesicle targeting
  • Vesicles are targeted to specific recipient compartments based on the presence of specific targeting signals (SNARE proteins, Rab GTPases)
  • Rab GTPases and tethering factors help guide vesicles to their target membranes
• Vesicle fusion
  1. SNARE proteins on the vesicle (v-SNAREs) and target membrane (t-SNAREs) interact to form a SNARE complex
  2. The formation of the SNARE complex brings the vesicle and target membrane into close proximity
  3. Membrane fusion occurs, allowing the release of vesicle contents (neurotransmitters, hormones) into the target compartment

Proteins for vesicle targeting

• SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor) proteins
  • v-SNAREs are located on the vesicle membrane
  • t-SNAREs are located on the target membrane
  • The formation of the SNARE complex is essential for membrane fusion and cargo delivery
• Rab GTPases
  • Small GTPases that cycle between GTP-bound (active) and GDP-bound (inactive) states
  • Rab proteins are involved in vesicle targeting and fusion
  • Different Rab proteins are associated with specific intracellular compartments (Rab5 for early endosomes, Rab7 for late endosomes) and help ensure the specificity of vesicle targeting
• Tethering factors
  • Large proteins or protein complexes that help tether vesicles to their target membranes
  • Tethering factors interact with Rab proteins and SNAREs to facilitate vesicle docking and fusion

Importance of vesicle fusion

• Neurotransmitter release
  • Synaptic vesicles containing neurotransmitters (glutamate, GABA) fuse with the presynaptic membrane at the active zone
  • The fusion of synaptic vesicles is triggered by calcium influx and is mediated by SNARE proteins
  • The release of neurotransmitters into the synaptic cleft allows for the transmission of signals between neurons
• Insulin secretion
  • Insulin-containing secretory granules in pancreatic beta cells fuse with the plasma membrane
  • The fusion of insulin granules is regulated by glucose levels and is mediated by SNARE proteins
  • Insulin secretion helps regulate blood glucose levels
• Exocytosis of digestive enzymes
  • Secretory vesicles containing digestive enzymes (amylase, lipase) fuse with the apical membrane of pancreatic acinar cells
  • The fusion of these vesicles releases digestive enzymes into the pancreatic ducts, which eventually lead to the small intestine
  • Digestive enzymes break down macromolecules in food for absorption