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Bulk transport

Endocytosis and exocytosis. Phagocytosis, pinocytosis, and receptor-mediated endocytosis.

Introduction

Imagine you are a macrophage: a merciless white blood cell that stalks, amoeba-like, through the tissues of the body, looking for pathogens, dead and dying cells, and other undesirables. When you encounter one of these, your task is not just to destroy it, but to devour it whole. (Chomp!)
This complete annihilation may seem a bit over the top, but it serves two useful purposes. First, it recovers valuable macromolecules for the body’s use. Second, in the case of foreign pathogens, it allows the macrophage to present fragments of the pathogen on its surface. This display alerts other immune cells that the pathogen is present and triggers an immune response.
Let’s take a step back, though. How does a macrophage “eat” a pathogen or a piece of cellular debris? In the past few sections, we’ve talked about ways that ions and small molecules, such as sugars and amino acids, can enter and exit the cell via channels and transporters. Channels and carrier proteins are great for letting specific small molecules cross the membrane, but they are too small (and too picky about what they transport) to let a cell take up something like an entire bacterium.
Instead, cells need bulk transport mechanisms, in which large particles (or large quantities of smaller particles) are moved across the cell membrane. These mechanisms involve enclosing the substances to be transported in their own small globes of membrane, which can then bud from or fuse with the membrane to move the substance across. For instance, a macrophage engulfs its pathogen dinner by extending membrane "arms" around it and enclosing it in a sphere of membrane called a food vacuole (where it is later digested).
Macrophages provide a dramatic example of bulk transport, and the majority of cells in your body don’t engulf whole microorganisms. However, most cells do have bulk transport mechanisms of some kind. These mechanisms allow cells to obtain nutrients from the environment, selectively “grab” certain particles out of the extracellular fluid, or release signaling molecules to communicate with neighbors. Like the active transport processes that move ions and small molecules via carrier proteins, bulk transport is an energy-requiring (and, in fact, energy-intensive) process.
Here, we’ll look at the different modes of bulk transport: phagocytosis, pinocytosis, receptor-mediated endocytosis, and exocytosis.

Endocytosis

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 a vesicle made out of plasma membrane.
There are variations of endocytosis, but all follow the same basic process. First, the plasma membrane of the cell invaginates (folds inward), forming a pocket around the target particle or particles. The pocket then pinches off with the help of specialized proteins, leaving the particle trapped in a newly created vesicle or vacuole inside the cell.
Endocytosis can be further subdivided into the following categories: phagocytosis, pinocytosis, and receptor-mediated endocytosis.

Phagocytosis

Phagocytosis (literally, “cell eating”) is a form of endocytosis in which large particles, such as cells or cellular debris, are transported into the cell. We’ve already seen one example of phagocytosis, because this is the type of endocytosis used by the macrophage in the article opener to engulf a pathogen.
Diagram illustrating phagocytosis.
Image modified from Openstax (original work by Mariana Ruiz Villareal).
Single-celled eukaryotes called amoebas also use phagocytosis to hunt and consume their prey. Or at least, they try to – the image series below shows a frustrated amoeba trying to phagocytose a yeast cell that’s just a tiny bit too big.
Once a cell has successfully engulfed a target particle, the pocket containing the particle will pinch off from the membrane, forming a membrane-bound compartment called a food vacuole. The food vacuole will later fuse with an organelle called a lysosome, the "recycling center" of the cell. Lysosomes have enzymes that break the engulfed particle down into its basic components (such as amino acids and sugars), which can then be used by the cell.
A series of 4 images shows a fluorescent amoeba trying to phagocytize a yeast cell. The first image shows the amoeba with ½ of the yeast cell ingested. The second image shows the amoeba with ¾ of the yeast cell ingested. The third image shows the amoeba extruding all but ¼ of the yeast cell, and the last image shows the yeast cell next to the amoeba after the yeast cell had been expelled from the amoeba.
Image credit: series of stills from video by Margaret Clarke1(Cell Image Library, CIL: 12654; Clarke et al., 2010).

Pinocytosis

Pinocytosis (literally, “cell drinking”) is a form of endocytosis in which a cell takes in small amounts of extracellular fluid. Pinocytosis occurs in many cell types and takes place continuously, with the cell sampling and re-sampling the surrounding fluid to get whatever nutrients and other molecules happen to be present. Pinocytosed material is held in small vesicles, much smaller than the large food vacuole produced by phagocytosis.
Diagrams depicting pinocytosis (left) and receptor-mediated endocytosis (right).
Images modified from OpenStax Biology (original work by Mariana Ruiz Villareal).

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, shown in the diagram above, is the best-studied coat protein2.
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 fluid2,3.
Although receptor-mediated endocytosis is intended to bring useful substances into the cell, other, less friendly particles may gain entry by the same route. Flu viruses, diphtheria, and cholera toxin all use receptor-mediated endocytosis pathways to gain entry into cells.
Suppose a certain type of molecule were removed from the blood by receptor-mediated endocytosis. What would happen if the receptor protein for that molecule were missing or defective?

Exocytosis

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.
Diagram illustrating the process of exocytosis.
Image modified from OpenStax Biology (original work by Mariana Ruiz Villareal).
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 interior4.

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  • male robot donald style avatar for user mary kh
    excuse me, can you tell me an example for pinocytosis ?
    (10 votes)
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  • duskpin sapling style avatar for user Juliana Clark
    Amino acids are monomers of proteins and proteins such as receptor proteins are involved. Does that mean that individual amino acids can enter a cell through receptor-mediated endocytosis?
    (7 votes)
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    • male robot hal style avatar for user kagiriallan0
      I am not fully sure, but I believe Receptor Mediated endocytosis means that the proteins act like an enzyme, meaning that only a specific macromolecule can fit into the receptor. An individual amino acid means that it cannot bind to the receptor because it does not fully meet the qualifications of the specific receptor. Imagine a password that scans your body to verify your entry. If you come one day without an arm(missing some amino acids), then the scan won't recognize, thus you won't enter. Similarly, receptor mediated endocytosis works this way. Hope this helps
      (10 votes)
  • leafers sapling style avatar for user M
    How exactly do pathogens use receptor mediated endocytosis to enter the cell?
    (7 votes)
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  • mr pink red style avatar for user Gabby Werner
    in the first paragraph, a white blood cell's "work" is described. What happens when there are not enough white blood cells?
    (6 votes)
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  • piceratops sapling style avatar for user Raven34567
    Are all the vesicles used in all bulk transport all coated in clathrin (or clathrin coated) or is it only in receptor-mediated endocytosis?
    (5 votes)
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    • hopper cool style avatar for user Arwick
      The formation of the clathrin-coating is vital in vesicle formation, clathrin causes the vesicle to form while SNARE proteins make sure that the vesicle will arrive in the right place.

      Vesicle formation without the clathrin mechanism seems possible (I found a paper discussing the possibilities from 1994: ''Endocytosis without clathrin'' by Sandvig and Deurs, you'll hit a paywall if you can't use a university proxy).

      That said however, clathrin does play a vital role and will be involved in (almost) all bulk transport.
      (9 votes)
  • leaf red style avatar for user Maya Aoude
    what is a real life example of endocytosis?
    (6 votes)
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  • blobby green style avatar for user Afiqah Jaafar
    Can a plant cell undergo endocytosis?
    (4 votes)
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  • marcimus orange style avatar for user Mango
    If macrophages devour pathogens, how do they make sure that they win the fight? What if they themselves get infected by the virus since penetration seems to be so easy?
    (3 votes)
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    • ohnoes default style avatar for user Prince
      Macrophages are a type of immune cell that plays a crucial role in the body's defense against pathogens, including viruses. While it is true that macrophages can be susceptible to infection by certain pathogens, they have developed several mechanisms to minimize the risk and maximize their effectiveness in fighting off invaders. Here are some key aspects:

      Recognition and Phagocytosis: Macrophages have surface receptors that can recognize specific molecules present on pathogens, such as viruses. Once a pathogen is detected, the macrophage engulfs it through a process called phagocytosis. This allows the macrophage to physically encapsulate and internalize the pathogen.

      Degradation: Once inside the macrophage, the pathogen is targeted for destruction. Macrophages have specialized compartments called lysosomes that contain enzymes capable of breaking down the internalized pathogens. This helps to neutralize and eliminate the infectious agents.

      Activation of Immune Response: Macrophages are capable of presenting antigens—fragments of the pathogens—to other immune cells, such as T cells. This presentation activates a more specific and potent immune response, coordinating the elimination of the pathogens.

      Antiviral Defense Mechanisms: Macrophages can release antiviral molecules, such as interferons, which can inhibit viral replication and spread. They also produce reactive oxygen species and nitric oxide, which have antimicrobial properties.

      While macrophages have these defense mechanisms, some highly adapted viruses can still evade or manipulate these responses, leading to macrophage infection. However, the immune system as a whole has multiple layers of defense. Other immune cells, such as T cells and natural killer cells, work together to eliminate infected macrophages and control the infection.

      Additionally, macrophages can activate a process called apoptosis, which is programmed cell death. If a macrophage detects that it is heavily infected and unable to eliminate the pathogen, it may undergo apoptosis to prevent the further spread of the infection.

      It's important to note that the immune response is a complex and dynamic process. The outcome of the fight between macrophages and pathogens depends on various factors, including the specific pathogen, the virulence of the infection, the overall immune status of the individual, and the coordination of the immune response.

      Hope that helped!
      (7 votes)
  • hopper jumping style avatar for user Yuya Fujikawa
    What is a transmembrane protein?
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  • duskpin seedling style avatar for user Pahal Shah
    Can't the cells use carrier proteins to move stuff out of it? Why does it spend energy and do exocytosis?
    (5 votes)
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