Molecule Transport: Exocytosis

Molecular Events of Exocytosis

  • Exocytosis involves the docking and fusion of secretory vesicles with the plasma membrane.
  • Key players include Rab proteins and their effectors, as well as SNARE proteins.
  • The process can be constitutive (continuous) or regulated (stimulus-dependent).

Rab Proteins and Effectors

  • Rab proteins are surface markers on transport vesicles, identifying their origin and cargo.
  • They act as motor proteins, moving along microtubules, and as tethering proteins, anchoring vesicles to the membrane.
  • Membrane receptors, known as Rab effectors, bind to Rab proteins.
  • Rab cascades can change the identity of organelles.

SNARE Proteins

  • SNARE proteins mediate membrane fusion.
  • v-SNAREs are located on vesicles, while t-SNAREs are on the target membrane.
  • The interaction between v-SNAREs and t-SNAREs promotes fusion by bringing membrane faces together and squeezing out water molecules.
  • This interaction releases energy and recruits other proteins to accelerate fusion.

SNARE Dissociation

  • NSF (N-ethylmaleimide-sensitive factor) cycles between the cytoplasm and membrane to dissociate SNAREs.
  • NSF, along with associated proteins (SNAPs), disassembles SNARE complexes, allowing them to function again.

Synaptic Signaling and Neurotransmission

  • Neurons communicate by releasing and receiving neurotransmitters.
  • Synaptic transmission involves the secretion of neurotransmitters by neurons, which then diffuse across the synaptic cleft to target cells.
  • Target cells must have receptors for the neurotransmitters.
  • Neurons have two types of vesicles: dense-cored secretory vesicles and small synaptic vesicles.

Neuron Shape and Function

  • An action potential occurs when a neuron sends information down the axon away from the cell body.
  • This involves the exchange of ions, with Na+Na^+ going in and K+K^+ going out.

Synaptic Vesicle Cycle

  • Synaptic vesicles wait near the membrane until signaled to release their contents.
  • Synaptic vesicles can form directly from endocytic vesicles, allowing for rapid and repeated responses.
  • For rapid exocytosis, synaptic vesicles are primed at the presynaptic plasma membrane.
  • Ca2+Ca^{2+} sensing protein Synaptotagmin releases complexin block, triggering neurotransmitter release.

Toxins Interfering with Neurotransmitter Release

  • Clostridium botulinum (“botox”) causes flaccid paralysis by preventing acetylcholine release and cleaving SNAREs.
  • Clostridium tetani (tetanus) causes paralysis by preventing GABA release and cleaving synaptobrevin (v-SNARE).
  • Latrodectus toxin (red back spider) triggers massive exocytosis of acetylcholine, adrenaline, GABA, and insulin, causing muscle contraction and degradation of vesicles.

Exosomes

  • Exosomes are tiny vesicles released into the extracellular space.
  • They originate from endosomes and multivesicular bodies.
  • Exosomes are secreted by various cell types and are involved in cellular communication, cancer progression, and control of the immune system.
  • They can be used as biomarkers for early detection methods and in cancer vaccines to stimulate the immune system.

Transcytosis

  • Transcytosis is the transport of macromolecules within a cell, from one side to the other.
  • Occurs in epithelial cells, endothelial cells, blood cells, and intestinal cells.
  • Example: transport of antibodies from mother’s milk across the gut epithelium, involving receptor-antibody complexes, recycling endosomes, and release into extracellular fluid.