ILK and Laminin-2 help oligodendrocytes to spread.

Myelination involves a vast spreading of cell membrane, but the mechanism underlying this is largely unknown. On page 397, Chun et al. show that laminin-2 induces cell spreading in oligodendrocytes, the myelinating cells of the CNS, by signaling through β1 integrins and integrin-linked kinase (ILK). They also resolve an apparent difference between mice and humans. In previous studies, humans with a defect in the laminin-2 gene have shown abnormalities in both the peripheral and central nervous systems, whereas laminin-2 mutant mice appeared to have only peripheral myelination defects. In the new study the authors show that, contrary to previous reports, myelination also fails in the central nervous system (CNS) of the mutant mice.

Although the CNS of the mutant mice appears normal by conventional microscopy, electron microscopy clearly reveals myelination defects in several large clusters of small-diameter axons. Laminin-2 induces a cascade of events in differentiated oligodendrocytes in culture, acting through β1 integrins and PI3- kinase to stimulate integrin-linked kinase and promote the dramatic cell spreading characteristic of myelinating oligodendrocytes. Chun et al. also found high levels of integrin-linked kinase expression in CNS oligoden-drocytes in vivo.

Since laminin-2 localizes to the surfaces of axons, its absence may prevent oligodendrocytes from spreading around certain CNS axons. In the areas of the laminin-2 mutant mouse CNS that are properly myelinated, other laminins may be able to substitute for laminin-2. ▪