Pinocytosis is a kind of endocytic process. It can define as the cellular mechanism where the bilayer cell membrane invaginates to form a sac to uptake the extracellular fluids and solutes into the cytoplasm. Pinocytosis is a spontaneous endocytic process which occurs in almost all the cells. It is prevalent in eukaryotes.
It also refers as “Cell drinking” or “Fluid phase endocytosis” that does not occur in a particular or specialized type of cell. Thus, pinocytosis merely refers as the cellular process that brings the extracellular fluid along with the solutes from cell surrounding into a cell cytosol.
Definition of Pinocytosis
Pinocytosis can define as a cellular mechanism where a cell intakes the extracellular fluid into the cytoplasm along with the suspended particles via pinocytic vesicles or pinosomes (<150 nm in diameter). In pinocytosis, cellular uptake can be selective or non-selective. Macropinocytosis and micropinocytosis (receptor-mediated) are the two mechanisms of pinocytosis, where a cell absorbs the extracellular material.
Process of Pinocytosis
Macropinocytosis and micropinocytosis are the two standard methods, depending upon the vesicle size and the amount of extracellular fluid enter into the cell.
It primarily uptakes the extracellular solutes from the extracellular fluid. Macropinocytosis is a non-selective cellular mechanism, which does not require cell receptors to mediate the endocytic pathway. However, it is a constitutive process for the primary innate immune cells like macrophages, dendritic cells, and monocytes etc. that are stimulated by the growth factors.
A cell undergoes remodelling of the actin cytoskeleton and extends to form an arm-like claw that later reconnects to develop a big vesicle refers as “Macropinosome”. Macropinocytosis is an actin driven endocytic mechanism, which was first introduced by a scientist named Warren Lewis in the year 1930. It involves the following sequential steps.
- A cell membrane ruffles when it finds the solute particles in the extracellular space. The signalling cascades include Rho-family GTPases that trigger the actin driven formation of membrane protrusions.
- The contents of the plasma membrane go through extensive deformation and initially forms a cup-like structure.
- Later, the distal ends of the cell membrane reconnect to form a big, phase bright macropinosome that having a diameter greater than 0.2-5 µm.
- Then the macropinosome undergoes maturation and fuses with the lysosome sac to form a mature, acidic and tubular macropinolysosome.
As macropinocytosis is a non-specific method, few pathogens may use macropinosome vesicle to reach their target cells.
Example: E.coli produce Shiga toxin, which can enter the target cell through the micropinosome in order to cause gastrointestinal complications.
It can define as the method, where the macromolecules of size less than 0.2 µm in diameter can be ingested and mediated by the clathrin-coated, caveolae-coated and uncoated vesicles.
In this method, the macromolecules bind to the cell surface receptors as a result of which the clathrin polymerizes around the cell membrane by the association of adaptor molecules. Clathrin can define as the triskelion molecules, which consists of one heavy and light chain with a molecular weight of 180 KDa and 35 KDa, respectively.
Towards the terminal end of clathrin chains, a globular domain is present, and the centre of the clathrin molecule refers as a vertex. A clathrin molecule appears as a “three-legged structure”. The adaptor molecules are generally of four types (AP-1, AP-2, AP-3 and AP-4), and these form a layer in between the clathrin lattice.
When a clathrin-coated bud forms, a cytosolic protein (dynamin) polymerizes over the neck of the invaginated pit. The dynamin protein releases complete clathrin-coated vesicle into the cytoplasm from the donor membrane by utilizing the energy derived from the GTP hydrolysis.
The complete clathrin-coated vesicle will then fuse with the early endosome as a result of which the clathrin coating will be shredded off by a process called “Uncoating”. Later, the early endosome will mature and turn more acidic that will result in a detachment of the ligand molecule from the cell receptor. The receptor will remain inside the endosome and transport back to the bilayer cell membrane for the process of recycling.
The ligand molecule residing inside the late endosome will then interfuse with the lysosome. Then, it will undergo degradation by the lysosomal enzymes. The lysosome will cause acidification of the ligand to break it down into simpler constituents and the undigested material will exocytose into the cell surrounding.
Example: Uptake of LDL by the LDL receptors into the clathrin/AP-2 coated vesicles having a diameter equal to 120 nm. The other example includes the internalization of ferrotransferrin by the transferrin receptor into a clathrin-coated sac.
Caveolae mediated pinocytosis
It is a clathrin-independent endocytic pathway that generally occurs in endothelial cells and adipocytes. Caveolae pits appear as the flask-like invagination and are rich in proteins plus lipids. Caveolins and cavins are the proteins that are the two primary elements of caveolae complex. In non-muscle cells, the Caveolin proteins are of two kinds, namely CAV-1 and CAV-2. The third kind of Caveolin (CAV-3) is muscle specific. Each caveola comprises a majority of CAV-1 molecules (around 140-150).
Cavins are the proteins that constitute the structural and functional component of caveolae. Mammalian cavin proteins are of three kinds, namely cavin-1 (PTRF), cavin-2 (SDPR) and cavin-3 (SRBC), while cavin-4 (MURC) is muscle specific. There are approximately 50 cavin proteins associated with each caveola.
The caveosomes are primarily formed and maintained by a protein named “Caveolin”. The caveolin protein comprises both cytoplasmic N and C terminals. Hydrophobic hairpin joins both the terminals. When a specific ligand binds with the cell surface receptor, the caveolin protein will cause a local change in the cell membrane.
A change in conformation of the cell membrane will lead to the formation of caveolae coated pits, which will eventually detach from the bilayer cell membrane to form a complete vesicle having a diameter of 80 nm. The caveosome will finally collapse with the lysosome.
Example: Albumin, folic-acid, cholera-toxin etc. are the cargo substances that are internalized via caveolae dependent endocytosis.
Pinocytosis performs the following primary tasks:
- It controls the cell volume and surface area to prevent the cell shrinking and swelling.
- It is a transportation method that involves the movement of macromolecules as well as micromolecules along with the extracellular fluid across the bilayer cell membrane.
- Pinocytosis provides the essentials nutrients and dissolved constituents to the cell through the degradation of macromolecules by the lysosomal enzymes.
Therefore, we can conclude that the pinocytosis is an endocytosis mechanism that ingests the molecules of the extracellular matrix into the cytoplasm via a pinocytic vesicle. This method of membrane transportation is less specific than the phagocytosis, as it mediates bulk transport.
Once the pinocytic vesicle pinches off from the bilayer cell membrane, it floats in the cytoplasm like a bubble. The vesicle can be passed undisturbed from one to the other cell, or it may fuse with the endocytic sac to release the dissolved nutrients into the cytoplasm so that the cell may utilize it.