The Tetraspanin KAI1/CD82 Is Expressed by Late-Lineage Oligodendrocyte Precursors and May Function to Restrict Precursor Migration and Promote Oligodendrocyte Differentiation and Myelination

Abstract

In the adult mammalian brain, oligodendrocyte progenitors can differentiate into mature oligodendrocytes during remyelination. Mechanisms that regulate migration and differentiation of progenitors are of great importance in understanding normal development and demyelinating/remyelinating conditions. In a microarray analysis comparing adult and neonatal O4-positive (ϩ) cells, we found that the tetraspanin KAI1/CD82 is far more highly expressed in adult O4 ϩ cells than in neonatal O4 ϩ cells (Lin et al., 2009). CD82 is a metastasis suppressor, and its expression is often downregulated or lost in the advanced stages of metastatic cancer. We hypothesized that CD82 could be a factor that restricts migration and promotes differentiation of maturing oligodendrocytes. Western blot analysis of isolated adult O4 ϩ cells confirms the elevated levels of CD82, which continues to be expressed as these become O1 ϩ in vitro. In the adult rat white matter, CD82 is coexpressed with CC1 and olig2 but not with NG2 or GFAP. Immature cells of the neonatal forebrain subventricular zone (SVZ) infected in vivo with a retrovirus that constitutively expresses CD82 do not remain immature but differentiate into either CC1ϩ and MBP ϩ myelinating oligodendrocytes in the white matter or zebrinII ϩ astrocytes in the cortex. Their migration from the SVZ is severely restricted. In contrast, downregulation of CD82 in SVZ cells in vivo, using retroviral-expressed short hairpin RNAs (shRNAs), prevents their differentiation into myelinating oligodendrocytes. shRNA-expressing cells remained PDGF receptor ␣ positive, olig2 ϩ , or NG2 ϩ or became CC1 ϩ nonmyelinating oligodendrocytes or GFAP ϩ astrocytes. CD82 thus appears to be a critical molecule in the regulation of oligodendrocyte progenitor migration and myelination.

Early Oligodendrocyte/Myelin Pathology in Alzheimer's Disease Mice Constitutes a Novel Therapeutic Target

“…Of note, previous reports have attributed CC-1 expression preferentially to nonmyelinating mature oligodendrocytes that lack MBP expression. 41 CC-1 expression is localized to the cell body of mature oligodendrocytes, whereas MBP is found predominantly within cellular processes of myelinating oligodendrocytes, making assessment of CC-1/MBP doublepositive cells by immunocytochemistry technically difficult.…”

Oligodendrogenesis in iron‐deficient rats: Effect of apotransferrin

“…O4 immunoreactivity at P11 [measured as integrated optical density (IOD)/mm 2 ] showed a complex situation. Given that O4 is a marker of different maturational stages of the OLGcs (from pre-OLGc to mature OLGc; Back et al, 2007;Mela and Goldman, 2009), in ID rats the majority of the label corresponds to the OPCs population, in that these cells failed to make progress to a more mature stage. On the contrary, in Co and ID aTf animals, O4 label corresponds not only to cells that remain as OPCs but also to mature stages of the linage.…”

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

“…CD82 is also expressed in late-lineage (O1-positive) oligodendrocyte precursors and appears to restrict the migration but promote the differentiation and myelination of these cells [106]. CD82 may inhibit c-Met and Rac1 activation in oligodendrocyte precursors and thereby overcomes the maturation-inhibitory effect of HGF on oligodendrocyte precursors [107].…”