Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. 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. Figure 1. In phagocytosis, the cell membrane surrounds the particle and engulfs it. 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 Figure 1.
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. Figure 2. In pinocytosis, the cell membrane invaginates, surrounds a small volume of fluid, and pinches off.
A variation of endocytosis is called pinocytosis. 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 Figure 2. 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.
Due to this functional diversity, endocytosis is a very active research area. In , Renate returned to Vienna and the Department of General and Experimental Pathology; first as a research associate, later as assistant professor.
In she obtained the venia docendi in Experimental Pathology and founded her own research group. Throughout her career, Renate Fuchs was fascinated by the many aspects of cellular uptake mechanisms. With more than 60 scientific publications, she significantly extended our knowledge on transporters, endosome acidification, endosome subpopulations, endocytic and transcytotic pathways of macromolecules, and cell entry mechanisms of viruses. Paying tribute to her work, collaborators and former students of Renate Fuchs contribute to this wmw issue.
It being impossible to entirely cover the broad range of endocytic topics, our scope is to give a flavor of the multifaceted world of endocytosis. His work was honored with a Nobel Prize in medicine in Metchnikoff was also the first to observe that endosomes were acidic compartments, as, during uptake of litmus particles, the cells turned from blue to red. Almost years later, it was shown that endosomes maintain an acidic internal pH as the result of the action of a membrane proton pump and that this acidification was required for proper endosomal sorting function.
Renate Fuchs was among the first researchers who investigated the mechanism of endosomal acidification and demonstrated that subpopulations of endosomes maintain distinct pH values [ 2 ]. This universal occurrence of endocytosis was proven in the s by electron microscopic studies of George Palade.
For about two decades, however, pinocytosis was assumed to be a nonspecific process that transported bulk fluid and solutes into cells.
In the s, the observation that nutrients and hormones bound to cells led to the assumption that cells have specific receptors on their surfaces designated for the uptake of extracellular molecules. The driving force behind the identification of this endocytic mechanism by Goldstein and Brown was the wish to unravel a human genetic disease, namely familial hypercholesterolemia FH. Finally, FH turned out to be caused by mutations in the LDL-receptor and a resulting inability to internalize cholesterol into cells, and Goldstein and Brown were honored with a Nobel Prize for their important discovery.
Meanwhile, endocytosis has been recognized as a multifactorial process, and the term now embraces distinct receptor-mediated as well as non-receptor-mediated uptake mechanisms. Moreover, various endocytic subcompartments involved in many distinct functions have been characterized. Elkin, Ashley M. Sandy Schmid and Renate Fuchs met at Yale University and collaborated on identification of endosome subpopulations and their acidification [ 2 , 3 ].
In this issue of wmw , Klaus-Peter Zimmer, along with J. Barone, and H. These include endocytosis and transcytosis of immunoglobulins and antibody—antigen complexes, a topic which was also of interest to Renate Fuchs [ 4 ]. In their article, Klaus-Peter Zimmer et al. Viruses, the smallest infectious agents, replicate only inside living cells of other organisms. While some animal viruses have the capacity to penetrate into the cytosol directly from the plasma membrane, most hijack the endocytic machinery of the host cell to enter the cytoplasm or nucleus depending on the replication strategy of the particular virus.
The common cold or AIDS are examples of human diseases caused by viruses, which affect many individuals. In his contribution to this wmw issue, Dieter Blaas from the Medical University of Vienna, Austria, summarizes early steps of viral infection including receptor recognition, diverse mechanisms of cellular uptake, and the uncoating of the viral genome.
What are common mistakes students make with endocytosis and exocytosis? What happens to a vesicle during exocytosis? Do endocytosis and exocytosis need energy? If so, where does the energy come from? What happens to a vesicle during endocytosis? How is a vesicle formed during endocytosis?
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