Cells can import and export large molecules across the plasma membrane. Macromolecules are secreted out from the cell by exocytosis and are ingested into the cell from outside through phagocytosis and endocytosis.
It is also called emeiocytosis and cell vomiting. In all eukaryotic cells, secretary vesicles are continually carrying new plasma membrane and cellular secretions such as proteins, lipids and carbohydrates (e.g., cellulose) from the Golgi apparatus to the plasma membrane or to cell exterior by the process of exocytosis. The proteins to be secreted are synthesized on the rough endoplasmic reticulum (RER). They pass into the lumen of the ER, glycosylated and are transported to the Golgi apparatus by ER-derived transport vesicles. In the Golgi apparatus the proteins are modified, concentrated, further glycosylated, sorted and finally packaged into vesicles that pinch off from trans-Golgi tubules and migrate to plasma membrane to fuse with it and release the secretion to cell’s exterior. In contrast, small molecules to be secreted (e.g., histamine by the mast cells) are actively transported from the cytosol (where they are synthesized on the free ribosomes) into preformed vesicles, where they are complexed to specific macromolecules (e.g., a network of proteoglycans, in case of histamine); so that, they can be stored at high concentration without generating an excessive osmotic gradient. During exocytosis, the vesicle membrane incorporates into the plasma membrane.
Endocytosis In endocytosis, small regions of the plasma membrane invaginate, until it has formed new intracellular membrane limited vesicles. In eukaryotes, the following types of endocytosis can occur.
The process of ingestion of large-sized solid substances (e.g., bacteria and parts of broken cells) by the cell is known as phagocytosis. The process of phagocytosis occurs in most protozoans and certain cells of multicellular organisms. In multicellular organisms such as mammals, the phagocytosis occurs very actively in granular leucocytes and in the cells of mesoblastic origin. The cells of the mesoblastic origin are collectively known as the cells of macrophagic or reticuloendothelial system. The cells of macrophagic system are histiocytes of the connective tissue, the reticular cells of the hemopoietic organs (bone marrow, lymph nodes, and spleen) and the endothelial cells which form the lining of capillary sinusoid of the liver, adrenal gland and hypophysis. The cells of macrophagic system can ingest bacteria, protozoa, cell debris or even colloidal particles by the process of phagocytosis.
Process of Phagocytosis
In phagocytosis, the target particle is first bound, to the specific receptors on the cell’s surface (process is called adsorption) and then the plasma membrane expands along the surface of the particle and eventually engulfs it. Vesicle formed by phagocytosis is called phagosome and it is typically 1 to 2 μm or larger in diameter, much larger than those formed during pinocytosis and receptor-mediated endocytosis. The phagosomes migrate to the interior of the cell and fuse with the pre-existing lysosomes (to form phagolysosome). The food is digested by the hydrolytic enzymes (acid hydrolase) of the lysosomes and the digested food is ultimately diffused to the surrounding cytoplasm. In addition to the normal set of lysosomal hydrolases, macrophage’s lysosomes contain enzymes that generate hydrogen peroxide (H2O2) and other toxic chemicals that aid in the killing of the bacteria. The undigested food is expelled from the plasma membrane by the process of ephagy or egestion. In macrophages, the undigested parts of ingested material such as the cell walls of microorganisms accumulate within lysosomes as residual bodies.
Opsonin An antibody or product of complement activation in blood serum that causes bacteria or other foreign cell to become more susceptible to the action of phagocytes
2. Pinocytosis is the non-specific uptake of small droplets of extracellular fluid by endocytic vesicles or pinosomes, having diameter of about 0.1μm to 0.2μm. Any material dissolved in the extracellular fluid is internalized in proportion to its concentration in the fluid.
3. Receptor-mediated endocytosis In this type of endocytosis, a specific receptor on the surface of the plasma membrane “recognizes” an extracellular macromolecule and binds it. The substance bound with the receptor is called the ligand. Examples of ligands may include viruses, low density lipoproteins (LDL), oligosaccharides, etc
The region of plasma membrane containing the receptor-ligand complex undergoes endocytosis. The whole process of receptor mediated endocytosis includes the following events
Interaction of ligands and cell surface receptors
The macromolecules (ligands) bind to complementary cell-surface receptors. There are more than 25 different types of receptors which are involved in receptor-mediated endocytosis of different types of molecules. Such a receptor is a trans-membrane protein which contains two specific binding sites.
- Ligand-binding site at the external surface of plasma membrane.
- Coated-pit binding site at the inner or cytosolic face of the plasma membrane.
Formation of coated-pits and coated-vesicles
The endocytic cycle begins at specialized regions of the plasma membrane, called coated-pits. Coated-pits are depressions of plasma membrane having a coat of bristle-like structure towards their cytosolic side. The ligand-loaded receptors diffuse into these coated-pits. A coated-pit may accommodate about 1000 receptors of assorted variety. In fact, coated-pits serve as molecular filters and selective concentrating devices, since, they tend to collect certain receptors and leave others. They increase the efficiency of internalization of a particular ligand more than 1000-fold and also carry minor components of extracellular fluid. The life-time of each coated-pit is quite short-within a minute or so of being formed, it invaginates into the cell and pinches off to form the coated-vesicles. The coat of coated pits and coated vesicles is made up of protein, called clathrin and certain other proteins. A molecule of clathrin is composed of three large polypeptide chains and three smaller polypeptide chains, all of which together form a three-legged structure, called triskelion. A number of triskelions assemble into a basket-like network of hexagons and pentagons on the cytoplasmic surface of the membranes.
Fusion of endocytic vesicle and endosome
Once a coated vesicle forms the clathrin and associated proteins dissociate from the vesicle membrane and return to the plasma membrane to form a new coated-pit. The resultant endocytic vesicle gets fused with pre-existing endosomes and ultimately its contents are utilized by the cell.