Endocytosis

What is Endocytosis?

The exchange of ions and molecules between neurons and their surroundings, which is the basis of signal transduction and various physiological activities, is realized through transmembrane and non-transmembrane cellular transportation. The non-transmembrane transportation is subdivided into exocytosis and endocytosis.

Endocytosis is a cellular process by which cells transfer materials that are too large to cross through the membrane lipid bilayer directly into cells, commonly like antibodies, microorganisms, and cell debris. When macromolecules are bound to the cell membrane surface, the local cell membrane invaginates and forms a small capsule surrounding macromolecules. Then the capsule that contains the macromolecules detaches from the cell membrane and forms a vesicle, entering the cell. Endocytosis is an important way for cells to obtain macromolecules and granules from the outside of the cell, which is closely related to a variety of biological processes, such as immune response, signal transduction, neurotransmitter transportation, cell and tissue metabolism balance.

Fig.1 The different types of endocytosis.

Endocytosis Pathways

According to the different substances and mechanisms, endocytosis is generally divided into three types: phagocytosis, pinocytosis, and receptor-mediated endocytosis.

1. Phagocytosis, or figuratively known as cell eating, is the process by which a cell internalizes large particles larger than 0.75 μm in diameter. In mammals, not only is phagocytosis a way for cells to obtain nutrients, but it is also an important way for the immune defense and immune balance. Some specialized phagocytes, such as macrophages and neutrophils, can ingest and destroy infected bacteria, viruses, damaged and aging cells through phagocytosis.
2. Pinocytosis, or referred as to cellular drinking, is a process that cells uptake the extracellular fluid or fat droplet. Pinocytosis usually occurs in highly ruffled regions of the plasma membrane where the local plasma membrane sinks to form a small nest to surround the droplet, and then pinches off from the plasma membrane to form vesicles and enters the cells.
3. Receptor-mediated endocytosis, a specialized type of pinocytosis, is a process by which cells specifically internalize or take up extracellular proteins or other compounds depending on receptors on the cell surface. This is the main pathway for uptake of biological macromolecules, including neurotransmitters, functional proteins, hormones, lymphokines, and so forth.

Fig.2 Phagocytosis, Pinocytosis, Receptor-mediated endocytosis.

Key Regulatory Factors of Endocytosis

Receptor-mediated endocytosis, also known as clathrin-mediated endocytosis, is the major endocytosis pathway, which plays an important role in intercellular signaling transduction, cell-extracellular protein extracellular proteins, and cellular homeostasis. As such an important biological pathway, it is strictly regulated by various factors, which mainly includes:

Clathrin and clathrin-adaptors

In the process of endocytosis, clathrin protein preferentially binds to the binding site of the cytoplasmic surface on the plasma membrane to participate in the formation of vesicles. Clathrin-adaptors, are vesicular transport adaptor proteins that bind clathrin to the adaptor complex on the surface of coated vesicles, playing important roles in the integration and transmission of intracellular signals.

Dynamin

Dynamin is a kind of GTPase aggregating in the neck of the endocytic vesicle, forming a helical polymer. During the endocytosis, it is mainly responsible for cutting the newly formed vesicles from the membrane of one cell compartment by hydrolysis of GTP.

Neuroligins

Neuroligins are a group of alternatively spliced transmembrane proteins distributing in the postsynaptic membranes. Through transsynaptic interactions with the neurexins, neuroligins are involved in the formation and consolidation of synapses between two neurons.

Synaptojanin

Synaptojanin is a family of proteins playing key roles in the uncoating and recovery of synaptic vesicles during the endocytosis in neurons, the possible mechanism of which is considered to be related to attracting the clathrin, associating with the vesicle coating.

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