Endocytosis is the import system of the cell where the macromolecules and particles from the surrounding medium is taken inside the cell. Cells internalize the materials by using plasma membrane components and
deliver them to an internal compartment called endosomes. From this endosomes they can be recycled to
same or different regions of the plasma membrane or can be delivered to
lysosomes for degradation.
There are three
types of endosomes in the cell,
Early
endosomes
Endosomes
which are found just beneath the plasma membrane which consists of the
components obtained directly from outside of the cell like carbohydrates, fats
etc. The components may go to the Golgi apparatus or may be transferred to the
lysosomes via late endosomes. In early endosomes, mild digestion may start,
hence many hydrolases are synthesized and delivered there as proenzymes called
Zymogens which contain extra inhibitory domains at their N terminus that keep
the hydrolases inactive until these domains are proteolytically removed.
Late
endosomes
Endosomes
which are found close to Golgi apparatus and near the nucleus. These are
actually intermediate between early endosomes and lysosomes.
Recycling
endosomes
Endosomes
which is found near the early endosome will be containing certain membrane
proteins or receptor. It will fuse with the plasma membrane when a signaling
molecule activates the signaling cascade which inturn activates the endosome to
bind to the cell membrane. After finishing their function, they will get back
to the cell as vesicle. Best example for this is the GLUT4 proteins which is
found inside the cell bounded to the vesicle.
Both the
late and early endosomes differ in their protein compositions and transition
from early to late endosomes is accompanied by the release of Rab5 and the
binding of Rab7.
The acidity
inside the late endosomes is higher compared to that of the earlier one. This
gradient of acidic environments has a crucial role in the function of these
organelles. Endosomes has a vascular H+
ATPase over the membrane which is responsible for making the vesicle acidic by
bringing in more amount of H+ ion. The pH basically in early endosomes is 6.
Coated
vesicles: They are having a distinctive cage of proteins covering their
cytosolic surface. Now before the vesicles fuse with a target membrane, they
discard their coat as it is required for the two cytosolic membrane surfaces to
interact directly and fuse.
The coat
has two functions,
1) It
concentrates specific membrane proteins in a specialized patch which then gives
rise to the vesicle membrane.
2) The
coat molds the forming vesicle.
These
proteins are assembles into a curved basketlike lattice that deforms the membrane
patch and thereby shapes the vesicle.
Three well
characterized types of coated vesicles distinguished by their coat proteins:
Clathrin
coated à
mediate transport from the endosomal-Golgi compartments and from the plasma
membrane.
COPII coated and COPI coated àmediate transport from the ER and Golgi cistern
Clathrin is
a coat protein whose subunits consists of three large and three small
polypeptide chains that together form a
three legged structure called triskelion. These triskelions assemble together
into a basketlike convex framework of hexagons and pentagons to form coated
pits on the cytosolic surface of membranes.
Adapter
protein which is a coat component in Clathrin coated vesicles form a discrete
second layer of the coated positioned between the Clathrin cage and the
membrane. They bind the Clathrin coat to the membrane and trap various
transmembrane proteins which include the transmembrane receptors that capture
soluble cargo molecules inside the vesicle so called cargo receptors.
Dynamins: These are the cytoplasmic proteins which helps in regulation of
pinch off and uncoating of coated vesicles.
The protein consists of PIP2 binding doman which tethers the protein to
the membrane and a GTPase domain, which regulates the rate at which the
vesicles pinch off from the membrane.
There are three types of Endocytosis:
- Phagocytosis
- Pinocytosis
- Receptor Mediated Endocytosis
Phagocytosis: large particles are
ingested via large vesicles called phagosome, which is about > 250 nm in
diameter. Phagosome end up in lysosomes and the products of the subsequent
digestive processes pass into cytosol to be used as food. Phagocytosis required
other than nutrition is carried out by specialized cells called professional
phagocytes. In mammals two main classes of professional phagocytes are
macrophages and neutrophils. Any indigestible particle inside the phagocytes
forms residual bodies which will be expelled out of the cell through
Exocytosis.
It’s a triggered process which
required the activation of receptors that transmit signals to the cell interior
and initiate the response. Eg: Antibodies triggers phagocytosis by exposing the
tail Fc region to the phagocytic cells.
Localized actin polymerization
initiated by Rho family GTPases and their activating Rho-GEFs shapes the
pseudopods. An active Rho GTPase switches on the kinase activity of local PI
kinases and initial actin polymerization occurs in response to an accumulation
of PIP2. To seal off the phagosome and complete its engulfment, actin is
depolymerized at its base as PIP2 is subject to a PIP3 kinase which converts it
into PIP3 is required for closure of the phagosome and may also contribute to
reshaping the actin network to help drive the invagination of the forming
phagosome.
Don’t eat me signal: the cell surface
protein binds to the inhibitory receptor of the phagocytic cell and recruits
tyrosine phosphatase proteins which antagonize the intracellular signals
required for the phagocytosis.
Eat me signal: Phosphatidyl serine
present inside the cell membrane will get exposed to the extracellular region
by the enzyme Flipase. The exposure will lead to the initiation of eat me
signal and macrophage will phagocytose the whole cell.
Pinocytosis: Fluid and solutes are
ingested via small pinocytic vesicles which are about 100 nm in diameter. This
process is a constitutive process where it occurs continuously regardless of
the needs of the cell. The pinocytic vesicles are formed from the coated pits
of the plasma membrane. The pits are mostly coated by Clathrin and it will be
pinched off from the membrane by dynamins.
Not all the pinocytic vesicle is
coated with Clathrin, but there are other vesicles which are not understood
very well and they are caveolae. They are recognized by their ability to
transport molecules across endothelial cells which form the inner lining of
blood vessels. They are thought to form from membrane microdomains or lipid
rafts. The major structural proteins in caveolae are caveolins which are
integral membrane proteins that each insert a hydrophobic loop into the
membrane from the cytosolic side but do not extend across the membrane. The caveolins don’t not dissociate like
Clathrin do because these proteins are integral proteins hence they stick with
the vesicle surface even after they are pinched off. Instead they are delivered
to the target compartments where they are maintained as discrete membrane
domains.
Receptor mediated endocytosis:
The macromolecules
bind to complementary transmembrane receptor proteins, accumulate in coated
pits and then enter the cell as receptor macromolecules complexes in clathrin
coated vesicles. This process is called receptor mediated endocytosis. This
happens basically because the ligands are selectively captured by receptors,
receptor mediated endocytosis provides a selective concentrating mechanism that
increases the efficacy of internalization of particular ligands more than a
hundred fold. The LDL receptor goes to the early endosome and gives off the
cholestrol molecules. Then retrives back to the plasma membrane without any
coating.
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