1: Braz J Med Biol Res. 2001 May;34(5):597-601.


Interactions of laminin with the amyloid beta peptide. Implications for Alzheimer's disease.

Morgan C, Inestrosa NC.

Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Extensive neuronal cell loss is observed in Alzheimer's disease. Laminin immunoreactivity colocalizes with senile plaques, the characteristic extracellular histopathological lesions of Alzheimer brain, which consist of the amyloid beta (A(beta)) peptide polymerized into amyloid fibrils. These lesions have neurotoxic effects and have been proposed to be a main cause of neurodegeneration. In order to understand the pathological significance of the interaction between laminin and amyloid, we investigated the effect of laminin on amyloid structure and toxicity. We found that laminin interacts with the A(beta)1-40 peptide, blocking fibril formation and even inducing depolymerization of preformed fibrils. Protofilaments known to be intermediate species of A(beta) fibril formation were also detected as intermediate species of laminin-induced A(beta) fibril depolymerization. Moreover, laminin-amyloid interactions inhibited the toxic effects on rat primary hippocampal neurons. As a whole, our results indicate a putative anti-amyloidogenic role of laminin which may be of biological and therapeutic interest for controlling amyloidosis, such as those observed in cerebral angiopathy and Alzheimer's disease.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 11323745 [PubMed - indexed for MEDLINE]

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2: Mol Neurobiol. 1996 Apr;12(2):95-116.


Role of laminin and integrin interactions in growth cone guidance.

McKerracher L, Chamoux M, Arregui CO.

Département de Pathologie, Université de Montréal, Quebec, Canada.

Laminin is well known to promote neuronal adhesion and axonal growth, but recent experiments suggest laminin has a wider role in guiding axons, both in development and regeneration. In vitro experiments demonstrate that laminin can alter the rate and direction of axonal growth, even when growth cone contact with laminin is transient. Investigations focused on a single neuronal type, such as retinal ganglion cells (RGCs), strongly implicate laminin as an important guidance molecule in development and suggest the involvement of integrins. Integrins are receptors for laminin, and neurons express multiple types of integrins that bind laminin. Morphologically, integrins cluster in point contacts, specialized regions of the growth cone that may coordinately regulate adhesion and motility. Recent evidence suggests that the structure and regulation of point contacts may differ from that of their nonneuronal counterpart, focal contacts. In part, this may be because the interaction of the cytoplasmic domain of integrin with the cytoskeleton is different in point contacts and focal contracts. Mutational studies where the cytoplasmic domain is truncated or altered are leading to a better understanding of the role of the alpha and beta subunit in regulating integrin clustering and binding to the cytoskeleton. In addition, whereas integrins may regulate motility through direct physical linkages to the growth cone cytoskeleton, an equally important role is their ability to elicit signaling, both through protein tyrosine phosphorylation and modulating calcium levels. Through such mechanisms integrins likely regulate the dynamic attachment and detachment of the growth cone as it moves on laminin substrates.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 8818145 [PubMed - indexed for MEDLINE]

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3: Kidney Int. 1993 Jan;43(1):66-72.


Role of laminin carbohydrates on cellular interactions.

Tanzer ML, Chandrasekaran S, Dean JW 3rd, Giniger MS.

Department of BioStructure and Function, University of Connecticut Health Center, Farmington.

Laminins, a family of large multidomain glycoproteins of the basal lamina, have been implicated in the development and maintenance of cellular and tissue organization. Considerable interest has arisen concerning the ways in which laminin carries out its biological functions. Previously these biologic responses have been primarily attributed to the peptide sequences of laminin, however, newer studies suggest that laminin carbohydrates may also participate in such cellular activities. Recently, a subpopulation of laminin molecules purified from EHS sarcoma by lectin affinity chromatography has been shown to contain about 25 to 30% carbohydrate. Most of the carbohydrates present are complex-type asparagine-linked oligosaccharides encompassing many different structures, some of which are unique to laminin. To date, the biological function of the carbohydrates of laminin remains somewhat unclear. They do not appear to be needed for heparin binding or to enhance proteinase stability, however, current evidence suggests they are important in cellular spreading and neurite outgrowth. It is our hypothesis that in the covalently-linked carbohydrate moieties of laminin will ultimately prove to be involved in information transfer to responsive cells. It is the purpose of this review to delineate current concepts of the structure and function of this unique glycoprotein's sugar chains.

Publication Types:
Review

PMID: 8433571 [PubMed - indexed for MEDLINE]

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4: Cell Differ Dev. 1990 Dec 2;32(3):377-81.


The expression and interactions of laminin in the developing nervous system.

Edgar D.

Department of Human Anatomy and Cell Biology, University of Liverpool, U.K.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 1983074 [PubMed - indexed for MEDLINE]

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5: Ciba Found Symp. 1984;108:25-43.


Laminin, proteoglycan, nidogen and collagen IV: structural models and molecular interactions.

Timpl R, Fujiwara S, Dziadek M, Aumailley M, Weber S, Engel J.

Major components of basement membranes, including collagen IV, laminin, heparan sulphate proteoglycan and nidogen, were isolated from the matrix of the EHS sarcoma. The purified components were analysed for their domain structure and for the participation of distinct domains in molecular interactions and cell binding. Collagen IV consists of four domains which have triple helical or non-collagenous structures. Self-assembly of the protein into a network-like organization occurs by specific interactions between N-terminal triple helical segments and between the C-terminal globules. Cell binding requires a central triple helical segment. Laminin has the shape of an asymmetrical cross; different globular domains within this structure mediate binding to proteoglycan and to cells. The proteoglycan consists of four heparan sulphate chains attached to a small protein core. These chains have the potential to bind laminin, fibronectin and collagen IV. Nidogen was isolated in several molecular forms which showed either self-aggregation or binding to laminin.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 6440757 [PubMed - indexed for MEDLINE]