All About Pinocytosis and Cell Drinking

Pinocytosis: Fluid-Phase Endocytosis

Pinocytosis is a cellular process by which fluids and nutrients are ingested by cells. Also called cell drinking, pinocytosis is a type of endocytosis that involves the inward folding of the cell membrane (plasma membrane) and the formation of membrane-bound, fluid-filled vesicles. These vesicles transport extracellular fluid and dissolved molecules (salts, sugars, etc.) across cells or deposit them in the cytoplasm. Pinocytosis, sometimes referred to as fluid-phase endocytosis, is a continual process that occurs in most cells and a non-specific means of internalizing fluid and dissolved nutrients. Since pinocytosis involves the removal of portions of the cell membrane in the formation of vesicles, this material must be replaced in order for a cell to maintain its size. Membrane material is returned to the membrane surface through exocytosis. Endocytotic and exocytotic processes are regulated and balanced in order to ensure that a cell's size remains relatively constant.

Pinocytosis Process

Pinocytosis is initiated by the presence of desired molecules in the extracellular fluid near the cell membrane surface. These molecules may include proteins, sugar molecules, and ions. The following is a generalized description of the sequence of events that occurs during pinocytosis.

Basic Steps of Pinocytosis

• The plasma membrane folds inward (invaginates) forming a depression or cavity that fills with extracellular fluid and dissolved molecules.
• The plasma membrane folds back on itself until the ends of the in-folded membrane meet. This traps the fluid inside the vesicle. In some cells, long channels also form extending from the membrane deep into the cytoplasm.
• Fusion of the ends of the in-folded membrane cuts the vesicle off from the membrane, allowing the vesicle to drift towards the center of the cell.
• The vesicle may traverse the cell and be recycled back into the membrane by exocytosis or may fuse with a lysosome. Lysosomes release enzymes that break open vesicles, emptying their contents into the cytoplasm to be utilized by the cell.

Micropinocytosis and Macropinocytosis

The uptake of water and dissolved molecules by cells occurs by two main pathways: micropinocytosis and macropinocytosis. In micropinocytosis, very small vesicles (measuring approximately 0.1 micrometers in diameter) are formed as the plasma membrane invaginates and forms internal vesicles that bud off from the membrane. Caveolae are examples of micropinocytotic vesicles that are found in the cell membranes of most types of body cells. Caveolae were first viewed in epithelial tissue that lines blood vessels (endothelium).

In macropinocytosis, vesicles larger than those formed by micropinocytosis are created. These vesicles hold larger volumes of fluid and dissolved nutrients. The vesicles range in size from 0.5 to 5 micrometers in diameter. The process of macropinocytosis differs from micropinocytosis in that ruffles form in the plasma membrane instead of invaginations. Ruffles are generated as the cytoskeleton reorders the arrangement of actin microfilaments in the membrane. The ruffles extend portions of the membrane as arm-like protrusions into the extracellular fluid. The ruffles then fold back on themselves enclosing portions of the extracellular fluid and forming vesicles called macropinosomes. Macropinosomes mature in the cytoplasm and either fuse with lysosomes (contents are released into the cytoplasm) or migrate back to the plasma membrane for recycling. Macropinocytosis is common in white blood cells, such as macrophages and dedritic cells. These immune system cells employ this pathway as a means of testing the extracellular fluid for the presence of antigens.

Receptor-mediated Endocytosis

While pinocytosis is a sound process for taking up fluid, nutrients, and molecules non-selectively, there are times when specific molecules are required by cells. Macromolecules, such as proteins and lipids, are taken up more efficiently by the process of receptor-mediated endocytosis. This type of endocytosis targets and binds specific molecules in extracellular fluid through the use of receptor proteins located within the cell membrane. In the process, specific molecules (ligands) bind to specific receptors on the surface of the membrane protein. Once bound, the target molecules are internalized by endocytosis. Receptors are synthesized by a cell organelle called the endoplasmic reticulum (ER). Once synthesized, the ER sends the receptors along to the Golgi apparatus for further processing. From there, the receptors are sent to the plasma membrane.

The receptor-mediated endocytotic pathway is commonly associated with regions of the plasma membrane that contain clatherine-coated pits. These are areas that are covered (on the side of the membrane facing the cytoplasm) with the protein clatherine. Once the target molecules bind to specific receptors on the membrane surface, the molecule-receptor complexes migrate toward and accumulate in clatherine-coated pits. The pit regions invaginate and are internalized by endocytosis. Once internalized, the newly formed clatherine-coated vesicles, containing fluid and desired ligands, migrate through the cytoplasm and fuse with early endosomes (membrane-bound sacs that help sort internalized material). The clatherine coating is removed and the vesicle's contents are directed toward their appropriate destinations. Substances acquired by receptor-mediated processes include iron, cholesterol, antigens, and pathogens.

Receptor-mediated Endocytosis Process

Receptor-mediated endocytosis allows cells to take up high concentrations of specific ligands from extracellular fluid without increasing the volume of fluid intake proportionately. It has been estimated that this process is greater than a hundred times more efficient at taking in selective molecules than pinocytosis. A generalized description of the process is described below.

Basic Steps of Receptor-mediated Endocytosis

• Receptor-mediated endocytosis begins as a ligand binds to a receptor on the plasma membrane.
• The ligand-bound receptor migrates along the membrane to a region containing a clatherine-coated pit.
• Ligand-receptor complexes accumulate in the clatherine-coated pit and the pit region forms an invagination that is internalized by endocytosis.
• A clatherine-coated vesicle is formed, which encapsulates the ligand-receptor complex and extracellular fluid.
• The clatherine-coated vesicle fuses with an endosome in the cytoplasm and the clatherine coating is removed.
• The receptor is enclosed in a lipid membrane and recycled back to the plasma membrane.
• The ligand remains in the endosome and the endosome fuses with a lysosome.
• Lysosomal enzymes degrade the ligand and deliver the desired contents to the cytoplasm.

Adsorptive Pinocytosis

Adsorptive pinocytosis is a non-specific form of endocytosis that is also associated with clatherine-coated pits. Adsorptive pinocytosis differs from receptor-mediated endocytosis in that specialized receptors are not involved. Charged interactions between molecules and the membrane surface hold the molecules to the surface at clatherine-coated pits. These pits only form for a minute or so before being internalized by the cell.

Sources

• Alberts, Bruce. “Transport into the Cell from the Plasma Membrane: Endocytosis.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 1 Jan. 1970, www.ncbi.nlm.nih.gov/books/NBK26870/. 
• Lim, J P, and P A Gleeson. “Macropinocytosis: an Endocytic Pathway for Internalising Large Gulps.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, Nov. 2011, www.ncbi.nlm.nih.gov/pubmed/21423264.