Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane,which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis and phagocytosis. It is a form of active transport.
The cytoskeleton is a complex,dynamic network of interlinking protein filaments present in the cytoplasm of all cells,including those of bacteria and archaea. In eukaryotes,it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components,microfilaments,intermediate filaments and microtubules,and these are all capable of rapid growth or disassembly dependent on the cell's requirements.
Microfilaments,also called actin filaments,are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin,but are modified by and interact with numerous other proteins in the cell. Microfilaments are usually about 7 nm in diameter and made up of two strands of actin. Microfilament functions include cytokinesis,amoeboid movement,cell motility,changes in cell shape,endocytosis and exocytosis,cell contractility,and mechanical stability. Microfilaments are flexible and relatively strong,resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces. In inducing cell motility,one end of the actin filament elongates while the other end contracts,presumably by myosin II molecular motors. Additionally,they function as part of actomyosin-driven contractile molecular motors,wherein the thin filaments serve as tensile platforms for myosin's ATP-dependent pulling action in muscle contraction and pseudopod advancement. Microfilaments have a tough,flexible framework which helps the cell in movement.
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton,and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells,where it may be present at a concentration of over 100 μM;its mass is roughly 42 kDa,with a diameter of 4 to 7 nm.
The Wiskott–Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system that in humans is encoded by the WAS gene. In the inactive state,WASp exists in an autoinhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon CDC42 and PIP2 acting to disrupt this interaction,causing the WASp protein to 'open'. This exposes a domain near the WASp C-terminus that binds to and activates the Arp2/3 complex. Activated Arp2/3 nucleates new F-actin.
Receptor-mediated endocytosis (RME),also called clathrin-mediated endocytosis,is a process by which cells absorb metabolites,hormones,proteins –and in some cases viruses –by the inward budding of the plasma membrane (invagination). This process forms vesicles containing the absorbed substances and is strictly mediated by receptors on the surface of the cell. Only the receptor-specific substances can enter the cell through this process.
The latrunculins are a family of natural products and toxins produced by certain sponges,including genus Latrunculia and Negombata,whence the name is derived. It binds actin monomers near the nucleotide binding cleft with 1:1 stoichiometry and prevents them from polymerizing. Administered in vivo,this effect results in disruption of the actin filaments of the cytoskeleton,and allows visualization of the corresponding changes made to the cellular processes. This property is similar to that of cytochalasin,but has a narrow effective concentration range. Latrunculin has been used to great effect in the discovery of cadherin distribution regulation and has potential medical applications. Latrunculin A,a type of the toxin,was found to be able to make reversible morphological changes to mammalian cells by disrupting the actin network.
Epsins are a family of highly conserved membrane proteins that are important in creating membrane curvature. Epsins contribute to membrane deformations like endocytosis,and block vesicle formation during mitosis.
Cortactin is a monomeric protein located in the cytoplasm of cells that can be activated by external stimuli to promote polymerization and rearrangement of the actin cytoskeleton,especially the actin cortex around the cellular periphery. It is present in all cell types. When activated,it will recruit Arp2/3 complex proteins to existing actin microfilaments,facilitating and stabilizing nucleation sites for actin branching. Cortactin is important in promoting lamellipodia formation,invadopodia formation,cell migration,and endocytosis.
Actin-related protein 3 is a protein that in humans is encoded by the ACTR3 gene.
Unconventional myosin-VI,is a protein that in humans is coded for by MYO6. Unconventional myosin-VI is a myosin molecular motor involved in intracellular vesicle and organelle transport.
Neural Wiskott–Aldrich syndrome protein is a protein that in humans is encoded by the WASL gene.
WAS/WASL-interacting protein (WIP) is a protein that in humans is encoded by the WIPF1 gene.
60S ribosomal protein L13 is a protein that in humans is encoded by the RPL13 gene.
Protein cordon-bleu is a protein that in humans is encoded by the COBL gene.
Bulk endocytosis refers to a form of endocytosis of synaptic vesicles at nerve terminals. In bulk endocytosis,compared to clathrin-mediated endocytosis,a larger area of presynaptic plasma membrane is internalised as cisternae or endosomes from which multiple synaptic vesicles can subsequently bud off. Bulk endocytosis is activated specifically during intense stimulation,such as during high-frequency trains of action potentials or in response to membrane depolarization by high extracellular concentrations of potassium.
Arp2/3 complex is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton-containing eukaryotic cells. Two of its subunits,the Actin-Related Proteins ARP2 and ARP3,closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70 degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion,phagocytosis,and intracellular motility of lipid vesicles.
In molecular biology,the cyclase-associated protein family (CAP) is a family of highly conserved actin-binding proteins present in a wide range of organisms including yeast,flies,plants,and mammals. CAPs are multifunctional proteins that contain several structural domains. CAP is involved in species-specific signalling pathways. In Drosophila,CAP functions in Hedgehog-mediated eye development and in establishing oocyte polarity. In Dictyostelium discoideum,CAP is involved in microfilament reorganisation near the plasma membrane in a PIP2-regulated manner and is required to perpetuate the cAMP relay signal to organise fruitbody formation. In plants,CAP is involved in plant signalling pathways required for co-ordinated organ expansion. In yeast,CAP is involved in adenylate cyclase activation,as well as in vesicle trafficking and endocytosis. In both yeast and mammals,CAPs appear to be involved in recycling G-actin monomers from ADF/cofilins for subsequent rounds of filament assembly. In mammals,there are two different CAPs that share 64% amino acid identity.
Rong Li is the Director of Mechanobiology Institute,a Singapore Research Center of Excellence,at the National University of Singapore. She is a Distinguished Professor at the National University of Singapore's Department of Biological Sciences and Bloomberg Distinguished Professor of Cell Biology and Chemical &Biomolecular Engineering at the Johns Hopkins School of Medicine and Whiting School of Engineering. She previously served as Director of Center for Cell Dynamics in the Johns Hopkins School of Medicine’s Institute for Basic Biomedical Sciences. She is a leader in understanding cellular asymmetry,division and evolution,and specifically,in how eukaryotic cells establish their distinct morphology and organization in order to carry out their specialized functions.
Kathryn Rachel Ayscough is a professor of molecular cell biology and head of the department of biomedical science at the University of Sheffield. She was awarded the 2002 Society for Experimental Biology President's Medal. Her research investigates the role of the actin cytoskeleton in membrane trafficking and cell organisation.
