Exocytosis Overview

Definition of Exocytosis
  - Exocytosis is the process by which a secretory vesicle or granule discharges its contents after fusing with the plasma membrane (PM).
  - Triggers for this process include an increase in the concentration of calcium ions [Ca2+].
  - The mechanism involves contacts between the vesicle and the plasma membranes, leading to the formation of a fusion pore.
  - Upon fusion, the luminal part of the vesicle membrane becomes the outer surface of the plasma membrane, while the cytosolic portion becomes part of the inner surface of the plasma membrane.

Release of Various Substances
  - Plasma cells release antibodies.
  - Fibroblasts release collagens.
  - Neurons secrete neurotransmitters.
  - T-cells produce perforin and granzyme.
  - Platelets release clotting factors.
  - Basophils secrete histamine.
  - β-cells produce insulin.

Key Molecules Involved:
  - Rab Proteins: Rab is a family of small GTPases involved in vesicle trafficking.
  - SNARE Complex: Composed of various proteins that mediate the fusion of membranes, specifically:
    - v-SNARE: Synaptobrevin (VAMP)
    - t-SNARE: Syntaxin, SNAP-25
  - Calcium Sensors: Include Synaptotagmin, which binds calcium and catalyzes vesicle fusion.
  - SM Proteins: Include Sec1/Munc18 which play a supportive role in SNARE complex assembly.
  - Other Proteins: Rab3, Rabphilin, Rho/Rac/Cdc42, Csp, RIM, NSF, Calmodulin, Arf, complexins, and synapsins.

Trigger Requirement:
- Regulated secretion requires a specific trigger for release, which differs based on cell type.
Storage of Secretory Products:
- Secretory products in regulated secretion are stored within larger secretory granules.
- In contrast, constitutive secretion involves smaller secretory vesicles.
Duration in Cytoplasm:
- Secretory products in regulated secretion remain in the cytoplasm longer compared to those in constitutive secretion.

Proteolytic Processing During Vesicle Formation:
  - Precursors of secretory proteins undergo proteolytic processing during the formation of secretory vesicles.
  - Example: Corticotropin (ACTH) undergoes processing:
    - Precursor -> B-lipotropin -> α-MSH -> y-lipotropin -> B-MSH -> B-endorphin

Mechanism Overview:
  - For efficient exocytosis, synaptic vesicles are primed at the presynaptic plasma membrane.
  - The process includes:
    1. Docking of the vesicle: Initiated by the interaction of v-SNARE (synaptobrevin) with t-SNARE (syntaxin and SNAP-25).
    2. Priming: Involves a series of conformational changes where partially assembled SNARE bundles prepare for fusion.
    3. Calcium Triggering: The binding of calcium ions at synaptotagmin binding sites instigates firing of the fusion process.
    4. Opening of Fusion Pore: The formation of a fusion pore facilitates neurotransmitter release into the synaptic cleft.
    5. Completion of Fusion: The vesicle merges fully with the plasma membrane, releasing neurotransmitters in response to action potential.

Origin: Synaptic vesicles can form directly from endocytic vesicles.
  - Key Steps Involved:
    1. Delivery of synaptic vesicle membrane components to the presynaptic plasma membrane.
    2. Endocytosis of synaptic vesicle membrane components to create new synaptic vesicles.
    3. Delivery of components to the endosome.
    4. Budding of new synaptic vesicles from the endosome.
    5. Loading neurotransmitters into synaptic vesicles.
    6. Secretion of neurotransmitters by exocytosis in response to an action potential.

Quick Removal of Secretory Vesicle Membrane Components:
- To maintain membrane integrity, secretory vesicle membrane components are promptly removed from the plasma membrane.
Role of Regulated Exocytosis:
- Some events of regulated exocytosis contribute to the enlargement of the plasma membrane, which is crucial for accommodating cellular growth and function.