Laminins structure

This short and selective review indicates that research into laminin structure and function has become increasingly sophisticated. The immediate future promises discovery of an increasing family of laminin isoforms, allowing the characterization of their biological activities, a more definitive map of the active domains and the peptides which subtend them, the working out of anti-laminin modulating influences, and characterisation of the receptors interacting with these domains in vivo to mediate cellular responses. Such study should clarify the contexts by which laminin exerts its powerful influence on neuronal development. 

The major components of the ECM are the structural proteins collagen, elastin, and fibrihin a number of specialized proteins (eg, fibronectin and laminin) and various proteoglycans. 

Cytoplasmic serine/threonine protein kinases catalyze the transfer of phosphate groups to serine and threonine residues of target proteins. Serine/threonine kinases have been recognized as the products of protooncogenes (e.g., c-mos, c-raj) or as kinases intimately involved with the regulation of serine/threonine kinase activity by cAMP. Some of these kinases specifically phosphorylate cellular structural proteins, such as histone, laminins, etc. Others phosphorylate still more kinases, resulting in either the activation or deactivation of downstream protein kinases. Specific examples in which serine/threonine kinases elicit specific cellular responses are discussed in this chapter. 

This technique has been described as a general method of studying protein-protein interactions as well as a method for investigating the three-dimensional structure of individual proteins (Muller et al., 2001 Back et al., 2003 Dihazi and Sinz, 2003 Sinz, 2003 Sinz, 2006). It also has been used for the study of the interactions of cytochrome C and ribonuclease A (Pearson et al., 2002), to investigate the interaction of calmodulin with a specific peptide binder (Kalkhof et al., 2005a Schmidt et al., 2005), and for probing laminin self-interaction (Kalkhof et al., 2005b). 

We have examined how cells maintain close control of CDK activity, but how does the activity of CDK control the cell cycle The list of target proteins that CDKs are known to act upon continues to grow, and much remains to be learned. But we can see a general pattern behind CDK regulation by inspecting the effect of CDKs on the structures of laminin and myosin and on the activity of retinoblastoma protein. 

The structure of the nuclear envelope is maintained in part by highly organized meshworks of intermediate filaments composed of the protein laminin. Breakdown of the nuclear envelope before segregation of the sister chromatids in mitosis is partly due to the phosphorylation of laminin by a CDK, which causes laminin filaments to depolymerize. 

Helix bundles. A third peptide chain can be added to a coiled coil to form a triple-stranded bundle.180-183 An example is the glycoprotein laminin found in basement membranes. It consists of three peptide chains which, for -600 residues at their C-terminal ends, form a three-stranded coil with heptad repeats.182184 Numerous proteins are folded into four helical segments that associate as four-helix bundles (Fig. 2-22).185-188 These include electron carriers, hormones, and structural proteins. The four-helix bundle not only is a simple packing arrangement, but also allows interactions between the + and - ends of the macro-dipoles of the helices. 

B) Electron micrographs of single molecules of laminin. (A) and (B) from Yurchenko and Schittny.663 663a Courtesy of Peter Yurchenko (C) Structural model of the three-chain laminin molecule with domain designations. From Beck et al.670 Domains I and II are a triplehelical coiled coil rod which, in the Bl chain, is interrupted by a small cysteine-rich domain a. Sites of cleavage by cathepsin are marked by arrows. 

Laminin [consisting of three polypeptide chains, A, Bl (possibly replaced in GBM by S) and B2] is the most important noncollagenous protein of the glomerular basement membrane. Laminin forms a second network, which is connected to the collagen IV network probably via another protein called entactin or nidogen. Laminin is probably very important for cellular differentiation and adhesion, but its mesh clearly also contributes to the structure of the glomerular basement membrane. The postnatally common embryonic laminin-10 isoform is... 

The MMPs are a family of zinc-dependent neutral endopep-tidases that share structural domains but differ in substrate specificity, cellular sources, and inductivity (Table I). All the MMPs are important for remodeling of the extra cellular matrix and share the following functional features (/) they degrade extracellular matrix components, including fibronectin, collagen, elastin, proteoglycans, and laminin, (//) they are secreted in a latent proform and require activation for proteolytic activity, (///) they contain zinc at their active site and need calcium for stability, (/V) they function at neutral pH, and (v) they are inhibited by specific tissue inhibitors of metalloproteinases (TIMPs). 

Cultures of primary cardiac myocytes (chick embryo) were formed on fibronectin patterned acrylic surfaces [198]. A microtextured PDMS chip with 20-urn-wide pegs was used to promote cell culture. After coating the PDMS chip with a thin layer of laminin, neonatal rat cardiac myocytes were cultured on it. The cultured cells are typically 50 p.m in length and 10-15 p.m in diameter. The PDMS chip was cast on a mold with parylene structures patterned on a Si wafer. Using the same mold, a poly(lactic/glycolic acid) (PLGA) chip could also be made for culture of rat cardiac fibroblasts [900]. 

A mouse neuronal cell line (PCC7-Mzl) was cultured on laminin deposited onto PS substrates using PDMS microcontact printing [901]. Growth of rat hippocampal neuron was found to be more favorable to closely spaced PS pillar structures [85]. 

---