Notes
Vesicular Transport Overview
Sections
3 pathways of vesicular transport
- Secretory pathway: delivers cargo to the plasma membrane.
- Endocytic pathway: uptake cargo from the plasma membrane.
- Retrieval pathway: recycles cellular molecules.
Key facts about vesicular transport:
- Compartment lumens mix via the transport intermediate.
- The membrane of each vesicle maintains its orientation.
- If the cell is growing, the secretory pathway is more active than the endocytic pathway.
Steps in secretory pathway
- Transport vesicles bud from the ER and carry content away from it to cis side of Golgi.
- Vesicular budding and fusion mediates the transport of cargo through the Golgi stacks, from cis to trans side.
- Cargo exits the Golgi via a transport vesicle on trans side.
- Transport vesicles fuse with plasma membrane or with endosomes (and then lysosomes).
Steps in endocytotic pathway
- Early endosome forms from plasma membrane and extracellular materials.
- Early endosome targets cargo to late endosomes.
- Late endosomes then deliver cargo to lysosomes, which degrade cargo.
The retrieval pathway takes several forms
- Endosomes can return cargo to the cell surface via recycling endosomes.
- Cargo in early and late endosomes can also return to the Golgi for reuse.
- Vesicles can deliver proteins from the trans face to the cis face of the Golgi.
- Vesicles can return proteins from the golgi to the ER as well.
3 steps of vesicular formation
- Cargo selection. Incorporation of cargo into a vesicle is carefully regulated to ensure that only the correct cargo gets transported.
- Vesicular budding. deformation of the hydrophobic membrane bilayer and breaking off of the membrane into a vesicle
- Vesicular targeting and fusion. Highly regulated just like cargo selection.
Cellular compartments are topologically equivalent when:
• Molecules can get from one to another without having to cross a membrane.
• Nuclear envelope, ER, Golgi, transport vesicles, endosomes, lysosomes, and extracellular space = topologically equivalent
Full-Length Text
- In this tutorial we will learn the general mechanism of vesicular transport: the means of transporting macromolecules (often referred to as "cargo") to and from the cell surface in membrane-bound vesicles (known as: transport vesicles).
- Start a table, so we can first establish the three main transport pathways within the cell.
- Denote that they include:
- The secretory pathway (aka exocytic pathway), in which cargo is directed out of the cell.
- The endocytic pathway, which involves transport of material from outside the cell (or the cell surface) into the cell.
- The retrieval pathway, which we will describe in detail shortly.
Now, let's illustrate each of these pathways.
To begin, we will draw the components of the endomembrane system.
- First, draw a section of the plasma membrane.
- Label extracellular space external to the plasma membrane.
- And the cytoplasm internal to the plasma membrane.
- Now let's draw the intracellular compartments of the cell as follows:
- First, draw a double-layered nuclear envelope.
- Label the nucleus.
- Then, show that the endoplasmic reticulum is continuous with the outer nuclear envelope.
- Finally, draw the Golgi apparatus as a series of cisternal stacks.
- Label the side of the Golgi that faces the nucleus cis and the side that faces the plasma membrane trans.
- Now, adjacent to the plasma membrane draw the following:
- Early endosome, which sorts cargo and redirects it to the cell surface or lysosomes.
- Late endosome, which targets cargo specifically to lysosomes.
- Lysosome, which is an acidic compartment that functions as the digestive organ for the cell.
- Now, show that the extracellular space and the luminal compartments within the cell are all topologically equivalent. - Recall that compartments are topologically equivalent if molecules can get from one to another without having to cross a membrane.
Now, let's use our diagram to illustrate the secretory and endocytic pathways; start with the secretory pathway.
- Step 1: Indicate that the endoplasmic reticulum synthesizes lipids and proteins.
- These proteins include water-soluble and membrane proteins.
- Step 2: Show that a transport vesicle buds from the ER and carries these proteins away from it.
- Water-soluble proteins remain suspended in the lumen and membrane proteins and lipids travel in the vesicular membrane.
- Indicate that the transport vesicle is topologically equivalent to the ER, the other membrane enclosed organelles and the extracellular space.
- Step 3: Indicate that the transport vesicle fuses with the Golgi apparatus.
- Step 4: The Golgi modifies, stores and secretes the cargo that it receives from the ER; it also synthesizes some of its own macromolecules.
- Step 5: Draw another transport vesicle adjacent to the Golgi stacks and use arrows to illustrate that vesicular budding and fusion mediates the transport of cargo through the Golgi stacks.
- Step 6: the cargo exits the Golgi via a transport vesicle (aka secretory vesicle) that buds from the organelle's trans face.
Now, illustrate that there are two possible pathways for step 7.
- Show that in one pathway, the transport vesicle fuses with the plasma membrane and releases its contents into the extracellular space
- Write that the secretory pathway is often referred to as the biosynthetic pathway because this process delivers cellular membrane components to the cell surface, which causes the membrane to grow.
- For the second pathway, indicate that the transport vesicle may also fuse with either the early or late endosome, thus delivering its contents to lysosomes.
- We will return to this concept when we illustrate the endocytic pathway.
- Denote that this secretory pathway is a form of exocytosis called constitutive exocytosis, which means that it is mediated by transport vesicles and is not highly regulated.
- Alternatively, exocytosis can also proceed via specialized vesicles called secretory vesicles. We learn the differences between these pathways elsewhere.
Now, let's illustrate the endocytic pathway.
- Use an arrow to show that an early endosome forms when the cell ingests extracellular materials.
- This cargo is first ingested into endocytic vesicles, and is then delivered to early endosomes where it is sorted.
- From here indicate that the early endosome targets cargo to late endosomes.
- Show that late endosomes then deliver cargo to lysosomes, which degrade cargo.
- Recall that transport vesicles from the Golgi also deliver cargo to lysosomes via early and late endosomes.
This brings us to our final pathway: the retrieval pathway.
- First, draw a recycling endosome between the early endosome and the cell surface.
- Use arrows to show that early endosomes can return cargo to the cell surface via recycling endosomes.
- Proteins such as signal receptors are recycled via this pathway.
- Show that cargo (such as membrane proteins) in early and late endosomes can also return to the Golgi for reuse. - Thus, membrane proteins from endocytic vesicles are recycled within the cell.
- Now draw another vesicle adjacent to the Golgi.
- Show that it can deliver proteins from the trans face to the cis face of the Golgi.
- Draw a final vesicle between the Golgi and the ER and show that proteins can be retrieved from the Golgi for return to the ER as well.
Now that we've illustrated all three pathways, let's summarize some major points about vesicular transport.
- Write that during vesicular transport:
- Compartment lumens mix via the transport intermediate. The transport intermediates we have drawn include transport vesicles and endosomes.
- The membrane of each vesicle maintains its orientation; thus, as we demonstrated, the vesicles, membrane enclosed organelles and extracellular space are topologically equivalent.
- If the cell is growing, the secretory pathway is more active than the endocytic pathway. Vesicular fusion with the cell membrane facilitates membrane growth.
Finally, let's briefly take a closer look at vesicular formation.
Write the following key steps that are common to all transport vesicles.
- Indicate that the first step is cargo selection. Incorporation of cargo into a vesicle is carefully regulated to ensure that only the correct cargo gets transported.
- Step two is vesicular budding, which involves deformation of the hydrophobic membrane bilayer and breaking off of the membrane into a vesicle.
- Step 3 is vesicular targeting and fusion, which is highly regulated just like cargo selection.
- Specialized proteins and receptors facilitate these steps, and use the retrieval pathway to return to their appropriate compartments after budding into vesicles.