Filamentous glycoproteins

Stress fibers are parallel bundles of actin filaments that develop in the cytoplasm of fibroblasts from the cortical actin network in response to mechanical tension. These often bind to the plasma membrane at focal contacts and, through transmembrane linker glycoproteins, to the extracellular matrix. Thus, actin filaments of stress fibers indirectly Join to the inner face of the plasma membrane through molecular assemblies of attachment proteins, which include an actin-capping protein, a-actinin, vinculin, and talin (Small, 1988). 

Fibronectin receptor is a two-chain glycoprotein of the integrin family that serves as a transmembrane linker by binding to talin on the cytoplasmic side and to fibronectin on the external side of the membrane. The pull exerted by stress fibers on attached structures may be produced by bipolar assemblies of nonmuscle myosin molecules producing a sliding of actin filaments of opposite polarity. 

Recent experiments have suggested that the tip link, a complex of two or three braided glycoprotein filaments [19], may be made in part from cadherin-23, a Ca2+-dependent cell-adhesion molecule [20], Moreover, cadherin-23 can interact directly or indirectly with myosin- lc, suggesting that these two molecules form part of the transduction complex in hair cells [20]. 

While one end of the dystrophin molecule binds to actin filaments, the C-terminal domain associates with several additional proteins to form a dystrophin-glycoprotein complex (see figure)/1 k Dystrophin is linked directly to the membrane-spanning protein P-dystroglycan, which in the outer membrane surfaces associates with a glycoprotein a-dystroglycan. The latter binds to laminin-2 (Fig. 8-33), a protein that binds the cell to the basal lamina. Four... 

Henderson, M., Polewski, R., Fanning, J. C., and Gibson, M. A. (1996). Microfibril-associated glycoprotein-1 (MAGP-1) is specifically located on the beads of the beaded-filament structure for fibrillin-containing microfibrils as visualized by the rotary shadowing technique./. Histochem. Cytochem. 44, 1389-1397. 

Figure 1. The muscle dystrophin-glycoprotein complex. The dystrophin-glycoprotein complex normally spans the plasma membrane of the skeletal muscle cell and may stabilize the sarcolemma and cytoskeleton to allow force transduction between the intracellular cytoskeleton (F-actin filaments) and the extracellular matrix. The molecules indicated are core components of the dystrophin-glycoprotein complex. Laminin 2 is the predominant laminin isoform in skeletal muscle basement membranes. Modified from McNeil and Steinhardt (2003)...

Rybakova, I.N., and Ervasti, J.M., 1997, Dystrophin-glycoprotein complex is monomeric and stabilizes actin filaments in vitro through a lateral association, J Biol Chem, 272, pp 28771-28778. 

In contrast, proteins vary markedly in their lateral mobility. Some proteins are nearly as mobile as lipids, whereas others are virtually immobile. For example, the photoreceptor protein rhodopsin (Section 32.3.1). a very mobile protein, has a diffusion coefficient of 0.4 pm s f The rapid movement of rhodopsin is essential for fast signaling. At the other extreme is fibronectin, a peripheral glycoprotein that interacts with the extracellular matrix. For fibronectin, D is less than 10-4 pm2 s f Fibronectin has a very low mobility because it is anchored to actin filaments on the inside of the plasma membrane through integrin, a transmembrane protein that links the extracellular matrix to the cytoskeleton. 

The major constituent of the extracellular plaques is amyloid -protein (Ap), which aggregates into 8 nm filaments. Ap is a peptide of 40 or 42 amino acid residues and is proteolytically derived from a transmembrane glycoprotein known as P-amyloid precursor protein (jSAPP). The enzymes that cleave APP to A/3 are known as sec-retases. SAPP is widely expressed, particularly in brain, and its gene has been localized to chromosome 21q. Two major observations have aided in understanding the role of Ap peptides in the pathology of Alzheimer s disease. The first is that patients with Down syndrome have trisomy 21... 

Schematic representation of cartilage proteoglycan. The monomers, consisting of glycosaminoglycan chains linked to a core protein by covalent linkage, extend laterally at intervals from opposite sides of a very long filament of hyaluronate. The interaction between the core protein and hyaluronate is noncovalent and is aided by the link protein. The entire structure is highly hydrated and occupies a large volume. [Reproduced with permission from W. J. Lennarz, The Biochemistry of Glycoproteins and Proteoglycans, Plenum Press, New York, 1980].

The amyloid-(3 peptide (A(3) has been identified as a 4 kDa hydrophobic nonglycosylated peptide consisting of 39 3 amino acid residues. It is derived by specific endoproteolytic cleavages from a 700 amino acid residue-long membrane-associated glycoprotein, named amyloid precursor protein (APP) (Citron et al., 1996 Dickson, 1997). A(3 appears in bundles of amyloid fibrils surrounded by abnormal neurites, and is believed to be the major component of the vascular and plaque filaments in individuals with AD, elderly people, and trisomy 21 carriers (Down s Syndrome) (Head and Lott, 2004). 

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