Water and small solutes enter and leave the cell by diffusing through the lipid bilayer of the plasma membrane or by being pumped or moved across the membrane by transport proteins. However, large molecules, such as proteins and polysaccharides, as well as larger particles, generally cross the membrane in bulk by mechanisms that involve packaging in vesicles. Like active transport, these processes require energy.
The main two modes of bulk transport across the membrane are endocytosis and exocytosis.
Endocytosis (endo = internal, cytosis = transport mechanism) is a general term for the various types of active transport that move particles into a cell by enclosing them in vesicle made out of plasma membrane.
There are different variations of endocytosis, but all share a common characteristic: The plasma membrane of the cell invaginates, forming a pocket around the target particle. The pocket pinches off, resulting in the particle being contained in a newly created intracellular vesicle formed from the plasma membrane.
Endocytosis can be further subdivided into the following categories: phagocytosis, pinocytosis, and receptor-mediated endocytosis.
Phagocytosis (the condition of “cell eating”) is the process by which large particles, such as cells or relatively large particles, are taken in by a cell. For example, when microorganisms invade the human body, a type of white blood cell called a neutrophil will remove the invaders through this process, surrounding and engulfing the microorganism, which is then destroyed by the neutrophil.
In preparation for phagocytosis, a portion of the inward-facing surface of the plasma membrane becomes coated with a protein called clathrin, which stabilizes this section of the membrane. The coated portion of the membrane then extends from the body of the cell and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane and the vesicle merges with a lysosome for the breakdown of the material in the newly formed compartment (endosome). When accessible nutrients from the degradation of the vesicular contents have been extracted, the newly formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane.
A variation of endocytosis is called pinocytosis. This literally means “cell drinking” and was named at a time when the assumption was that the cell was purposefully taking in extracellular fluid. In reality, this is a process that takes in molecules, including water, which the cell needs from the extracellular fluid. Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle does not need to merge with a lysosome.
A variation of pinocytosis is called potocytosis. This process uses a coating protein, called caveolin, on the cytoplasmic side of the plasma membrane, which performs a similar function to clathrin. The cavities in the plasma membrane that form the vacuoles have membrane receptors and lipid rafts in addition to caveolin. The vacuoles or vesicles formed in caveolae (singular caveola) are smaller than those in pinocytosis. Potocytosis is used to bring small molecules into the cell and to transport these molecules through the cell for their release on the other side of the cell, a process called transcytosis.
- Receptor-mediated Endocytosis
Receptor-mediated endocytosis is a form of endocytosis in which receptor proteins on the cell surface are used to capture a specific target molecule. The receptors, which are transmembrane proteins, cluster in regions of the plasma membrane known as coated pits. This name comes from a layer of proteins, called coat proteins, that are found on the cytoplasmic side of the pit. Clathrin, is the best-studied coat protein.
When the receptors bind to their specific target molecule, endocytosis is triggered, and the receptors and their attached molecules are taken into the cell in a vesicle. The coat proteins participate in this process by giving the vesicle its rounded shape and helping it bud off from the membrane. Receptor-mediated endocytosis allows cells to take up large amounts of molecules that are relatively rare (present in low concentrations) in the extracellular fluid.
Some human diseases are caused by the failure of receptor-mediated endocytosis. For example, the form of cholesterol termed low-density lipoprotein or LDL (also referred to as “bad” cholesterol) is removed from the blood by receptor-mediated endocytosis. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood, because their cells cannot clear LDL particles from their blood as it will stay in the fluid and increase in concentration.
Cells must take in certain molecules, such as nutrients, but they also need to release other molecules, such as signaling proteins and waste products, to the outside environment. Exocytosis (exo = external, cytosis = transport mechanism) is a form of bulk transport in which materials are transported from the inside to the outside of the cell in membrane-bound vesicles that fuse with the plasma membrane.
Some of these vesicles come from the Golgi apparatus and contain proteins made specifically by the cell for release outside, such as signaling molecules. Other vesicles contain wastes that the cell needs to dispose of, such as the leftovers that remain after a phagocytosed particle has been digested.
These vesicles are transported to the edge of the cell, where they can fuse with the plasma membrane and release their contents into the extracellular space. Some vesicles fuse completely with the membrane and are incorporated into it, while others follow the “kiss-and-run” model, fusing just enough to release their contents (“kissing” the membrane) before pinching off again and returning to the cell interior.
In eukaryotes there are two types of exocytosis:
- Ca2+ triggered non-constitutive (i.e., regulated exocytosis)
- Non-Ca2+ triggered constitutive (i.e., non-regulated)
Ca2+ triggered non-constitutive exocytosis requires an external signal, a specific sorting signal on the vesicles, a clathrin coat, as well as an increase in intracellular calcium. Exocytosis in neuronal chemical synapses is Ca2+ triggered and serves interneuronal signalling.
Constitutive exocytosis is performed by all cells and serves the release of components of the extracellular matrix or delivery of newly synthesized membrane proteins that are incorporated in the plasma membrane after the fusion of the transport vesicle.