Endocytosis

Endocytosis is a cellular process in which substances are brought into the cell. The material to be
internalized is surrounded by an area of cell membrane, which then buds off inside the cell to
form a vesicle containing the ingested material. Endocytosis includes pinocytosis (cell drinking)
and phagocytosis (cell eating). It is a form of active transport.

Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated

endocytosis (also known as clathrin-mediated endocytosis), caveolae, pinocytosis, and
phagocytosis.

 Clathrin-mediated endocytosis is mediated by the production of small (approx. 100 nm in

diameter) vesicles that have a morphologically characteristic coat made up of the
cytosolic protein clathrin. Clathrin-coated vesicles (CCVs) are found in virtually all cells
and form domains of the plasma membrane termed clathrin-coated pits. Coated pits can
concentrate large extracellular molecules that have different receptors responsible for the
receptor-mediated endocytosis of ligands, e.g. low density lipoprotein, transferrin, growth
factors, antibodies and many others.
 Caveolae are the most commonly reported non-clathrin-coated plasma membrane buds,
which exist on the surface of many, but not all cell types. They consist of the cholesterol-
binding protein caveolin (Vip21) with a bilayer enriched in cholesterol and glycolipids.
Caveolae are small (approx. 50 nm in diameter) flask-shape pits in the membrane that
resemble the shape of a cave (hence the name caveolae). They can constitute up to a third
of the plasma membrane area of the cells of some tissues, being especially abundant in
smooth muscle, type I pneumocytes, fibroblasts, adipocytes, and endothelial cells.Uptake
of extracellular molecules is also believed to be specifically mediated via receptors in
caveolae.
 Potocytosis is a form of receptor-mediated endocytosis that uses caveolae vesicles to
bring molecules of various sizes into the cell. Unlike most endocytosis that uses caveolae
to deliver contents of vesicles to lysosomes or other organelles, material endocytosed via
potocytosis is released into the cytosol.
 Pinocytosis, which usually occurs from highly ruffled regions of the plasma membrane, is
the invagination of the cell membrane to form a pocket, which then pinches off into the
cell to form a vesicle (0.5-5 µm in diameter) filled with a large volume of extracellular
fluid and molecules within it (equivalent to ~100 CCVs). The filling of the pocket occurs
in a non-specific manner. The vesicle then travels into the cytosol and fuses with other
vesicles such as endosomes and lysosomes.
 Phagocytosis is the process by which cells bind and internalize particulate matter larger
than around 0.75 µm in diameter, such as small-sized dust particles, cell debris,
microorganisms and apoptotic cells. These processes involve the uptake of larger
membrane areas than clathrin-mediated endocytosis and caveolae pathway.
More recent experiments have suggested that these morphological descriptions of endocytic
events may be inadequate, and a more appropriate method of classification may be based
upon the clathrin-dependence of particular pathways, with multiple subtypes of clathrin-
dependent and clathrin-independent endocytosis. Mechanistic insight into non-phagocytic,
clathrin-independent endocytosis has been lacking, but a recent study has shown how Graf1
regulates a highly prevalent clathrin-independent endocytic pathway known as the
CLIC/GEEC pathway.
Exocytosis
Exocytosis is the process of moving materials from within a cell to the exterior of the cell. This
process requires energy and is therefore a type of active transport. Exocytosis is an important
process of plant and animal cells as it performs the opposite function of endocytosis. In
endocytosis, substances that are external to a cell are brought into the cell.

In exocytosis, membrane-bound vesicles containing cellular molecules are transported to the cell
membrane. The vesicles fuse with the cell membrane and expel their contents to the exterior of
the cell. The process of exocytosis can be summarized in a few steps.

Basic Process of Exocytosis:

1. Vesicles containing molecules are transported from within the cell to the cell membrane.
2. The vesicle membrane attaches to the cell membrane.
3. Fusion of the vesicle membrane with the cell membrane releases the vesicle contents
outside the cell.
Exocytosis serves several important functions as it allows cells to secrete waste substances and
molecules, such as hormones and proteins. Exocytosis is also important for chemical signal
messaging and cell to cell communication. In addition, exocytosis is used to rebuild the cell
membrane by fusing lipids and proteins removed through endocytosis back into the membrane.

Exocytotic vesicles containing protein products are typically derived from an organelle called the
Golgi apparatus, or Golgi complex. Proteins and lipids synthesized in the endoplasmic reticulum
are sent to Golgi complexes for modification and sorting. Once processed, the products are
contained within secretory vesicles, which bud from the trans face of the Golgi apparatus.

Other vesicles that fuse with the cell membrane do not come directly from the Golgi apparatus.
Some vesicles are formed from early endosomes, which are membrane sacs found in the
cytoplasm. Early endosomes fuse with vesicles internalized by endocytosis of the cell membrane.
These endosomes sort the internalized material (proteins, lipids, microbes, etc.) and direct the
substances to their proper destinations. Transport vesicles bud off from early endosomes sending
waste material on to lysosomes for degradation, while returning proteins and lipids to the cell
membrane. Vesicles located at synaptic terminals in neurons are also examples of vesicles that
are not derived from Golgi complexes.

There are three common pathways of exocytosis. One pathway, constitutive exocytosis, involves
the regular secretion of molecules. This action is performed by all cells. Constitutive exocytosis
functions to deliver membrane proteins and lipids to the cell's surface and to expel substances to
the cell's exterior.

Regulated exocytosis relies on the presence of extracellular signals for the expulsion of materials
within vesicles. Regulated exocytosis occurs commonly in secretory cells and not in all cell
types. Secretory cells store products such as hormones, neurotransmitters, and digestive enzymes
that are released only when triggered by extracellular signals. Secretory vesicles are not
incorporated into the cell membrane but fuse only long enough to release their contents. Once the
delivery has been made, the vesicles reform and return to the cytoplasm.

A third pathway for exocytosis in cells involves the fusion of vesicles with lysosomes. These
organelles contain acid hydrolase enzymes that break down waste materials, microbes, and
cellular debris. Lysosomes carry their digested material to the cell membrane where they fuse
with the membrane and release their contents into the extracellular matrix.

Exocytosis occurs in four steps in constitutive exocytosis and in five steps in regulated
exocytosis. These steps include vesicle trafficking, tethering, docking, priming, and fusing.

 Trafficking: Vesicles are transported to the cell membrane along microtubules of the
cytoskeleton. Movement of the vesicles is powered by the motor proteins kinesins,
dyneins, and myosins.
 Tethering: Upon reaching the cell membrane, the vesicle becomes linked to and pulled
into contact with the cell membrane.
  Docking: Docking involves the attachment of the vesicle membrane with the cell
membrane. The phospholipid bilayers of the vesicle membrane and cell membrane begin
to merge.
 Priming: Priming occurs in regulated exocytosis and not in constitutive exocytosis. This
step involves specific modifications that must happen in certain cell membrane molecules
for exocytosis to occur. These modifications are required for signaling processes that
trigger exocytosis to take place.
 Fusion: There are two types of fusion that can take place in exocytosis. In complete
fusion, the vesicle membrane fully fuses with the cell membrane. The energy required to
separate and fuse the lipid membranes comes from ATP. The fusion of the membranes
creates a fusion pore, which allows the contents of the vesicle to be expelled as the
vesicle becomes part of the cell membrane. In kiss-and-run fusion, the vesicle
temporarily fuses with the cell membrane long enough to create a fusion pore and release
its contents to the exterior of the cell. The vesicle then pulls away from the cell
membrane and reforms before returning to the interior of the cell.

Exocytosis versus Endocytosis

While exocytosis is a form of active transport that moves substances and materials from a cell's
interior to the exterior of the cell, endocytosis, is the mirror opposite. In endocytosis, substances
and materials that are outside of a cell are transported into the interior of the cell. Like
exocytosis, endocytosis requires energy so is also a form of active transport.

Like exocytosis, endocytosis has several different types. The different types are similar in that
the basic underlying process involves the plasma membrane forming a pocket or invagination
and surrounding the underlying substance that needs to be transported into the cell. There are
three major types of endocytosis: phagocytosis, pinocytosis, as well as receptor mediated
endocytosis.