Biomedical subjects

L Lohikangas

Publications and source records attributed to L Lohikangas.

4 recordsLinked to original sources

PubMed1998

Integrins during muscle development and in muscular dystrophies.

Cellular interactions with the extracellular matrix (ECM) have been shown to be important for a number of developmental events from the time of fertilization up till the maturation of the organism. In the following review we will discuss what is currently known about these interactions with special emphasis on the role of integrins during the formation of skeletal muscle. The importance of cell-ECM interactions will also be illustrated by a discussion of what happens when these interactions go awry, as happens in muscular dystrophies.

Animals↗

PubMed1998

Mouse myoblasts can fuse and form a normal sarcomere in the absence of beta1 integrin expression.

Antibody perturbation experiments suggested that migration, terminal differentiation and fusion of myoblasts are dependent on beta1 integrin expression. In addition, several studies have postulated that beta1 integrins have a role in the formation of sarcomeres. In the present report we have analysed skeletal myogenesis in wild-type/beta1-null chimeric mice and beta1-null embryoid bodies. Trunk and limbs of beta1-null chimeric mice contained muscle tissue composed of normal and beta1-null myoblasts indicating that all myotomic sublineages can form, migrate to their peripheral targets and fuse in the absence of beta1 integrin expression. Pure populations of beta1-null myoblasts and satellite cells isolated from beta1-null chimeric embryos and chimeric newborn mice, respectively, were able to differentiate in vitro and to fuse into multinucleated myotubes. Quantitative and qualitative comparisons between normal and beta1-null myoblasts revealed no apparent difference in their capacity to terminally differentiate and fuse. Furthermore, beta1-null myotubes developed sarcomeres which were indistinguishable from wild-type controls. When normal and beta1-null ES cells were differentiated into embryoid bodies, they contained fully differentiated myotubes with normal sarcomeres and normal deposition of costameric components. However, formation of beta1-null myotubes was delayed and was less efficient in beta1-null embryoid bodies than in wild-type controls. High expression of alphav integrin subunit at the tips of normal as well as beta1-null myotubes indicated that the lack of beta1 integrins did not result in a significant redistribution of alphav-containing receptors.

Animals↗

PubMed1997

Fibronectin-integrin interactions.

Fibronectin is recognized by at least ten cell surface receptors of the integrin family. Most cell types in the body can adhere to fibronectin via these receptors, and thereby fibronectin becomes involved in many different biological processes. Three areas related to fibronectin and its receptors which have developed rapidly during the last few years are summarized in this review: the mechanisms of interactions between fibronectin and integrins, fibronectin polymerization, and in vivo functions of the proteins as studied by gene targeting in mice.

Animals↗

PubMed1996

Beta 1 integrin-dependent and -independent polymerization of fibronectin.

The mouse cell line GD25, which lacks expression of the beta 1 family of integrin heterodimers due to disruption of the beta 1 integrin subunit gene, was used for expression of full-length cDNA coding for splice variant A of the mouse beta 1 integrin subunit. In a stably transformed clone (GD25-beta 1A), the expressed protein was found to form functional heterodimeric receptors together with the subunits alpha 3, alpha 5, and alpha 6. Both GD25 and GD25-beta 1A attached to fibronectin and formed focal contacts which contained alpha v beta 3, but no detectable alpha 5 beta 1A. The presence of GRGDS peptide allowed alpha 5 beta 1A to locate to focal contacts of GD25-beta 1A cultured on fibronectin, while the beta 1-null GD25 cells were unable to attach under these conditions. Affinity chromatography revealed that alpha 5 beta 1A and alpha v beta 3 could bind to a large cell-binding fragment of fibronectin. alpha 5 beta 1A strongly promoted polymerization of fibronectin into a fibrillar network on top of the cells. Whereas little alpha v beta 3 was colocalized with the fibronectin fibrils in GD25-beta 1A cells, this integrin was able to support fibronectin fibril polymerization in GD25 cells. However, the alpha v beta 3-induced polymerization was less efficient and occurred mainly in dense cultures of the GD25 cells. Thus, while both alpha 5 beta 1A and alpha v beta 3 are able to support adhesion to fibronectin, alpha v beta 3 dominates in the formation of focal contacts, and alpha 5 beta 1A has a prime function in fibronectin matrix assembly. This is the first report on fibronectin matrix assembly in the absence of beta 1 integrins.

Animals↗