Tetraspanins, such as CD81, can form lateral associations with each other and with other transmembrane proteins. These interactions may underlie CD81 functions in multiple cellular processes, such as adhesion, morphology, migration, and differentiation. Since CD81's role in neuronal cells’ migration has not been established, we here evaluated effects of CD81 on the migratory phenotype of SH-SY5Y neuroblastoma cells. CD81 was found enriched at SH-SY5Y cell's membrane, co-localizing with its interactor filamentous-actin (F-actin) in migratory relevant structures of the leading edge (filopodia, stress fibers, and adhesion sites). CD81 overexpression increased the number of cells with a migratory phenotype, in a potentially phosphatidylinositol 3 kinase (PI3K)–Ak strain transforming (AKT) mediated manner. Indeed, CD81 also co-localized with AKT, a CD81-interactor and actin remodeling agent, at the inner leaflet of the plasma membrane. Pharmacologic inhibition of PI3K, the canonical AKT activator, led both to a decrease in the acquisition of a migratory phenotype and to a redistribution of intracellular CD81 and F-actin into cytoplasmic agglomerates. These findings suggest that in neuronal-like cells CD81 bridges active AKT and actin, promoting the actin remodeling that leads to a motile cell morphology. Further studies on this CD81-mediated mechanism will improve our knowledge on important physiological and pathological processes such as cell migration and differentiation, and tumor metastasis.

Neuronal migration is guided by long radially oriented glial fibres. During late stages of development radial glial cells are transformed into astrocytes. A predominant intermediate filament protein within radial glial cells and immature astrocytes is vimentin. In this study fetal brain sections were used to demonstrate the transient features of vimentin-positive radial glia. In the lower half of the cerebral wall of the 6th gestational month bundles, curvature, and crossing of vimentin-positive fibres are regularly seen. Moreover, fibres terminating on vessels are observed. In the upper half fibres are radially oriented; when ascending towards the pial surface the number and diameter of fibres appears conspicuously decreased. Radially aligned fibres display numerous varicosities. In the 8th month the bulk of vimentin-positive fibres is encountered next to the ganglionic eminence and below isocortical cerebral fissures. The dentate gyrus is conspicuous due to its high amount of immunolabelled fibres. Furthermore, densely packed fibres are visible within the internal and external capsule and in the vicinity of the anterior commissure. Radial glial somata are found in the proliferative areas as well as in the adjacent white matter. In the latter location bipolar, monopolar and stellate vimentin-positive cells are present. The results demonstrate an area-specific distribution pattern of vimentin-positive structures which can be correlated with migrational events. Areas maturing late in development for instance, reveal dense immunolabelling in the 8th month. The orientation and position of radial fibres point to an additional developmental role of these fibres, i.e. their involvement in the guidance of growing axons. Moreover, the arrangement and morphology of vimentin-positive fibres, such as retraction of fibres or occurrence of varicosities, are indicative of degenerative events. Accordingly, a transformation of radial glial somata, their displacement towards the white matter and finally the growth of stellate processes can clearly be demonstrated.