The tetraspanin KAI1/CD82 is expressed by late-lineage oligodendrocyte precursors and may function to restrict precursor migration and promote oligodendrocyte differentiation and myelination.

Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.

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 (+) cells, we found that the tetraspanin KAI1/CD82 is far more highly expressed in adult O4(+) cells than in neonatal O4(+) 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(+) cells confirms the elevated levels of CD82, which continues to be expressed as these become O1(+) 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 CC1(+) and MBP(+) myelinating oligodendrocytes in the white matter or zebrinII(+) 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 alpha positive, olig2(+), or NG2(+) or became CC1(+) nonmyelinating oligodendrocytes or GFAP(+) astrocytes. CD82 thus appears to be a critical molecule in the regulation of oligodendrocyte progenitor migration and myelination.

在成年哺乳动物大脑，髓鞘再生时少突胶质前体细胞可以分化为成熟的少突胶质细胞。了解调节脱髓鞘/髓鞘再生时少突胶质前体细胞迁移与分化的机制非常重要。利用基因芯片分析比较成年与新生的O4+细胞，我们发现四次跨膜蛋白KAI1/CD82与幼年相比在成年O4+细胞表达很高。CD82是一种转移抑制子，在转移癌中它的表达经常下调或者丢失。我们假设CD82是抑制迁移促进少突胶质细胞分化的因子。Western blot 分析成年的O4+细胞证实了CD82表达增多，它可以在离体的O1+细胞表达。在成年大鼠脑白质，CD82与CC1 和Olig2双标，但不与NG2、GFAP双标；利用标记CD82逆转录病毒感染新生鼠前脑的侧脑室下区（SVZ）。白质中，它不在未成熟少突表达，而是在分化为成熟的CC1+和MBP+的髓鞘化少突胶质细胞上表达，皮层上斑纹蛋白⁺的星形胶质细胞表达。它们从SVZ的迁移非常有限。相反，利用逆转录病毒的短链RNA下调SVZ的CD82蛋白，可以阻止SVZ的CD82细胞分化为髓鞘化的少突胶质细胞。短发卡RNA表达的细胞表达PDGFR-alpha+,Olig2+,或NG2+，或者变成CC1+的非髓鞘化的少突胶质细胞或GFAP+的少突胶质细胞。CD82是调解少突胶质前体细胞迁移髓鞘形成的关键分子。

J Neurosci. 2009 Sep 9;29(36):11172-81.