Laminin isoforms in development and disease

Abstract

The members of the laminin family of heterotrimers are major constituents of all basement membranes, sheet-like extracellular structures, present in almost all organs. The laminins bind to cell surface receptors and thereby tightly connect the basement membrane to the adjacent cell layer. This provides for the specific basement membrane functions to stabilize cellular structures, to serve as effective physical barriers, and furthermore, to govern cell fate by inducing intracellular signalling cascades. Many different types of diseases involve basement membranes and laminins. Metastasizing solid tumors must pass through basement membranes to reach the vascular system, and various microbes and viruses enter the cells through direct interaction with laminins. Furthermore, whereas mutations in one specific laminin chain lead to a muscular disorder, mutations of other laminin chains cause skin blistering and kidney defects, respectively. This review summarizes recent progress concerning the molecular mechanisms of laminins in development and disease. The current knowledge may lead to clinical treatment of lamininopathies and may include stem-cell approaches as well as gene therapy.

Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4

“…Laminin is heterotrimer protein containing  and  chains, and formerly, lamin 1 to 15 were identified but currently they are re-named by using the chain number [25,26]. Laminin 5 (currently laminin 332 as 3, 3, and 2) is known to associated with various cancers, and especially it is involved in human glioblastomas through integrin 31 as cellular receptor [27].…”

Extracellular matrix in the trabecular meshwork

“…Laminins have a cruciform shape composed of a heterotrimer of different isoforms of α, β and γ subunits. (Scheele et al 2007) The central shaft of the cross is a long coiled-coil formed by interaction of α-helix domains in the three subunits. The arms and head are formed by the individual subunits.…”

“…The cellular laminin receptors include a number of integrins, the α-subunit of dystroglycan, specific HS GAG chains and sulfatides. (Scheele et al 2007) Nidogen/entactin is a glycoprotein that binds to laminin and is thought to link it to type IV collagen as part of stabilizing basement membrane ECM networks. (Gersdorff et al 2007) Nidogen 1 is expressed in TM.…”

Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives

“…Different laminins have their own spatial and temporal expression. In a recent review on the role of laminins in physiological and pathogenic conditions, schéele et al 53 reported that one of the specific basement membrane functions is "to govern cell fate by inducing intracellular signalling cascades". In fact the broad spatial distribution of laminin genes products offers tissue specificity as each tissue has its proper ligands.…”

“…They concluded that this novel form of therapy requires more studies to define the nucleotide context of PTCs, the mechanism of mrNA stability and its translation into a functional protein. Finally, the future treatment of lamininopathies may include stem-cell approaches as well as gene therapy 53 .…”