Protein cytoskeletal

Jellinger KA. Movement disorders with tau protein cytoskeletal pathology. Parkinson s disease. In Stern GM, ed. Advances in Neurology. Vol. 80. Philadelphia Lippincott, Williams Wilkins, 1999 393-311. 

Mechanical functions of cells require interactions between integral membrane proteins and the cyto-skeleton. These functions include organization of signaling cascades, formation of cell junctions and regulation of cell shape, motility, endo- and exocytosis. Several different families of membrane-associated proteins mediate specific interactions among integral membrane proteins, cytoskeletal proteins and contractile proteins. Many of these linker proteins consist largely of various combinations of conserved protein-association domains, which often occur in multiple variant copies. 

The last part of this account will be devoted to protein kinases and protein phosphatases and some recent results we have obtained for them. Protein kinases and phosphatases are signaling biomolecules that control the level of phosphorylation and dephosphorylation of tyrosine, serine or threonine residues in other proteins, and by this means regulate a variety of fundamental cellular processes including cell growth and proliferation, cell cycle and cytoskeletal integrity. 

Certain proteins endow cells with unique capabilities for movement. Cell division, muscle contraction, and cell motility represent some of the ways in which cells execute motion. The contractile and motile proteins underlying these motions share a common property they are filamentous or polymerize to form filaments. Examples include actin and myosin, the filamentous proteins forming the contractile systems of cells, and tubulin, the major component of microtubules (the filaments involved in the mitotic spindle of cell division as well as in flagella and cilia). Another class of proteins involved in movement includes dynein and kinesin, so-called motor proteins that drive the movement of vesicles, granules, and organelles along microtubules serving as established cytoskeletal tracks. ... 

Two cytoskeletal proteins, tltln (also known as connectm) and nebulm, account for 15% of the total protein in the myofibril. Together these proteins form a flexible filamentous network that surrounds the myofibrils. Titin is an elastic protein and can stretch under tension. Its discovery and characteriza-... 

Cytoskeletal proteins Titin 1 2800 10 A-I interaction Links myosin filament... 

The ankyrin repeat motif is one of the most common protein-protein interaction domains. Ankyrin repeats are modules of about 33 amino acids repeated in tandem. They are found in a large number of proteins with diverse cellular functions such as transcriptional regulators, signal transducers, cell-cycle regulators, and cytoskeletal proteins. 

Cytokeratins are members of the intermediate filament class of cytoskeletal proteins. Cytokeratins are a large protein family comprising two subfamilies of polypeptides, i.e. acidic (type I) and basic (type II) ones. Cytokeratin form tetramers, consisting of two type I and two type II polypeptides arranged in pairs of laterally aligned coiled coils. The distribution of the different type I and II cytokeratins in normal epithelia and in carcinomas is differentiation-related and can be used for cell typing and identification. 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

The major types of cytoskeletal filaments are 7-nm-thick microfilaments. 25-nm-thick microtubules, and 10-nm-thick intermediate filaments (IPs). These are respectively composed of actin, tubulin, and a variety of interrelated sparsely soluble fibrous proteins termed intermediate filament proteins. In addition, thick myosin filaments are present in large numbers in skeletal and heart muscle cells and in small numbers in many other types of eukaryotic cells. 

Studies on muscle contraction carried out between 1930 and 1960 heralded the modem era of research on cytoskeletal stmctures. Actin and myosin were identified as the major contractile proteins of muscle, and detailed electron microscopic studies on sarcomeres by H.E. Huxley and associates in the 1950s produced the concept of the sliding filament model, which remains the keystone to an understanding of the molecular mechanisms responsible for cytoskeletal motility. 

Microtubules (MT) are the largest of the cytoskeletal filaments with an outer diameter of about 25 nm, a wall thickness of about 5 nm, and a central lumen measuring about 15 nm. They consist of tubulin and associated proteins. Vertebrate brain tissue is a rich source of extractable tubulin because of the large numbers of microtubules that are present in axons and dendrites. Tubulin obtained from such a natural source is a heterodimer of 100 kD composed of a-tubulin and P-tubulin. Brain a-tubulin is a globular polypeptide that contains 451 amino acid residues, whereas P-tubulin, which is somewhat shorter, is made up of 445 amino acid residues. These two molecular species of tubulin share in common 40% of their amino acid residues. 

Dynein, kinesin, and myosin are motor proteins with ATPase activity that convert the chemical bond energy released by ATP hydrolysis into mechanical work. Each motor molecule reacts cyclically with a polymerized cytoskeletal filament in this chemomechanical transduction process. The motor protein first binds to the filament and then undergoes a conformational change that produces an increment of movement, known as the power stroke. The motor protein then releases its hold on the filament before reattaching at a new site to begin another cycle. Events in the mechanical cycle are believed to depend on intermediate steps in the ATPase cycle. Cytoplasmic dynein and kinesin walk (albeit in opposite... 

Bundles of parallel actin filaments with uniform polarity. The microvilli of intestinal epithelial cells (enterocytes) are packed with actin filaments that are attached to the overlying plasma membrane through a complex composed of a 110-kD protein and calmodulin. The actin filaments are attached to each other through fimbrin (68 kD) and villin (95 kD). The actin bundles that emerge out of the roots of microvilli disperse horizontally to form a filamentous complex, the terminal web, in which several cytoskeletal proteins, spectrin (fodrin), myosin, actinin, and tropomyosin are present. Actin in the terminal web also forms a peripheral ring, which is associated with the plasma membrane on the lateral surfaces of the enterocyte (see Figure 5, p. 24). 

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