Cytotoxicology Studies of 2-D Nanomaterials
Suresh C. Pillai, Yvonne Lang in Toxicity of Nanomaterials, 2019
Clathrin-coated vesicles are utilised to internalise NMs of size usually <100 nm. It is a receptor-mediated endocytosis pathway, where the plasma membrane undergoes inward budding and forms vesicles. The vesicles are layered with various protein receptors permitted to internalise the specific molecule (Sorkin and Puthenveedu, 2013). In this energy-dependent process the clathrin does not interact with the membrane or the ingested particles. It completely depends on the protein receptors and the accessory proteins present on the walls of the vesicles. The accessory proteins are the cytoplasmic proteins which are later subjected to reuse for another endocytosis cycle. The internalised NMs experience organization in the endosomes and are later sent to the surface or delivered to other mature endosomes like lysosomes (McMahon and Boucrot, 2011). The uptake of nutrients, activation of signalling pathways, regulation of surface expression of proteins, and retrieval of proteins deposited after vesicle fusion are some of the functions associated with clathrin-mediated endocytosis (Chen et al., 1998; Liu et al., 2001; McMahon and Boucrot, 2011; Motley et al., 2003; Sikora et al., 2017).
Absorption of Macromolecules by Mammalian Intestinal Epithelium
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Coated pits and vesicles are involved in receptor-mediated endocytosis.17,50 Clathrin, with a molecular weight 180,000, is the major structural protein of coated pits and vesicles.50,54 Clathrin defines the cytoplasmic side of endocyotic organelles by enclosing them in a lattice of pentamers and haxamers. Finally, a polyhedral vesicle is produced. In receptor-mediated endocytosis, it is believed that specific protein receptors are randomly dispersed in the lipid bilayer of the plasmalemma.49 To initiate internalization, the macromolecule or the ligand binds to its receptor. This in turn promotes the binding of clathrin to the other end of the receptor next, ligand-receptor-clathrin complexes cluster at the base of the microvillus, causing the plasmalemma to invaginate or pit. The coated pit pinches off forming a coated submicroscopic vesicle that then traverses the cell and fuses with the basal lateral membrane. Finally, the microvesicle undergoes reverse pincocytosis (exocytosis), resulting in the discharge of the ligand into extracellular space.70,72
Imaging of Intracellular Targets
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
Large and hydrophilic molecules can enter the cell through different types of endocytosis, a process by which cells absorb molecules by invagination of the plasma membrane. Substances may be taken up by endocytosis after binding to a receptor, by interacting with other structures on the cell surface, or just by being engulfed together with fluid surrounding the cell when an endocytic vesicle is formed. There are multiple types of endocytic pathways of which the clathrin-mediated endocytosis pathway is best known and by far the best studied. Additionally, several clathrin-independent endocytosis mechanisms have been described (Sandvig et al. 2008; Howes et al. 2010; Kumari et al. 2010), including dynamin-dependent mechanisms and dynamin-independent mechanisms. It should be noted that receptor-mediated endocytosis can involve several of the aforementioned mechanisms, dependent on the type of receptor being used.
Human ovarian granulosa cells use clathrin-mediated endocytosis for LDL uptake: immunocytochemical and electron microscopic study
Published in Ultrastructural Pathology, 2023
Aynur Abdulova, Merjem Purelku, Hakan Sahin, Gamze Tanrıverdi
Regarding the clathrin-mediated endocytic pathway, an important component is the clathrin protein. Clathrin-coated vesicles have a three-layered structure consisting of an outer region formed by clathrin proteins in the form of a cage, an intermediate region consisting of a lipid membrane, as well as internal adaptor proteins (APs).8 Along with clathrin, more than 60 other cytosolic proteins are involved in the formation of clathrin-coated endocytic vesicles.9 All these proteins assemble from the cytosol to the endocytic region in a highly ordered manner. The collected vesicles are transported to the target site by SNARE (N-ethylmaleimide-sensitive factor binding protein receptor) proteins. SNAREs manage the transfer of material to be transported during vesicular transport. In an animal cell, there are at least 20 different organelle-associated SNARE proteins, each attached to a specific membrane involved in the biosynthetic-secretion or endocytic pathway. These proteins function as transmembrane proteins and are referred to as vesicular SNAREs (v-SNAREs) with characteristic spiral domains.10
Protein transduction domain of translationally controlled tumor protein: characterization and application in drug delivery
Published in Drug Delivery, 2022
Endocytosis is largely classified as a two part process that includes phagocytosis and pinocytosis. Pinocytosis, the uptake of fluid and solute by the cell, occurs in all types of cells through four pathways including (i) clathrin-mediated, (ii) caveolae-mediated, (iii) clathrin, caveolae-independent pathway, and (iv) macropinocytosis (Conner & Schmid, 2003). Clathrin-mediated endocytosis (CME) is a clathrin/dynamin-dependent, receptor-mediated process and this pathway is reported to operate in the cases of TAT-PTD, oligoarginine, and anionic PTDs (Ruseska & Zimmer, 2020). Binding of ligand to a specific receptor on the cell membrane induces the assembly of clathrins in a polyhedral lattice, followed by the invagination of clathrin-coated membrane surface (Ruseska & Zimmer, 2020). Caveolae-mediated endocytosis (CvME) is mediated by the formation of caveolae, a highly hydrophobic membrane domain rich in sphingolipid and cholesterol (Ruseska & Zimmer, 2020) and is reported to occur with TAT fusion protein, transportan and proline-rich PTDs. Actin cytoskeleton and cholesterol are the essential elements for caveolae formation and dynamin, a multidomain GTPase, constricts the neck of caveolae for enabling its release (Ruseska & Zimmer, 2020).
Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review
Published in Tissue Barriers, 2022
Idris Zubairu Sadiq, Aliyu Muhammad, Sanusi Bello Mada, Bashiru Ibrahim, Umar Aliyu Umar
Several clathrin-independent endocytosis routes mainly rely on caveolin-enclosed cholesterol-rich rafts to form invaginations of the caveolin membrane, whereas the clathrin-dependent endocytosis is composed of the protein clathrin, functioning as the main component of the endocytic vesicle coat, and is the most commonly recognized endocytic pathway67,70(Figure 2). Macropinocytosis is a type of endocytosis that eventually led to the internalization of fluids and membranes in large vacuoles through an endocytic actin-dependent pathway (Figure 2), thus creating a structure similar to a cup that closes to form a relatively large macropinosome.71 Macropinocytosis is an evolutionarily conserved type of endocytosis through nonselective uptake usually triggered in mammalian cells by growth factor-mediated stimulation of pathways PI3K and Ras.72 As Ras and PI3K become active, actin polymerization and membrane ruffling are facilitated by Rac1 and Rab5 small GTPases and PAK1 kinase, which influence the development and closure of macropinosomes.72–75 Compared to direct penetration, the endocytosis approach has the advantage of being faster because it uses energy and is more likely to move bulk materials in the shortest time possible.
Related Knowledge Centers
- Chromosome 17
- Chromosome 22
- Cytoplasm
- Protein
- Vesicle
- Cell Membrane
- Exocytosis
- Endocytosis
- C-Terminus
- N-Terminus