| First Author | Ly PTT | Year | 2018 |
| Journal | J Cell Sci | Volume | 131 |
| Issue | 15 | PubMed ID | 29991512 |
| Mgi Jnum | J:264673 | Mgi Id | MGI:6194402 |
| Doi | 10.1242/jcs.212076 | Citation | Ly PTT, et al. (2018) PTPalpha is required for laminin-2-induced Fyn-Akt signaling to drive oligodendrocyte differentiation. J Cell Sci 131(15):jcs212076 |
| abstractText | Extrinsic signals that regulate oligodendrocyte maturation and subsequent myelination are essential for central nervous system development and regeneration. Deficiency in the extracellular factor laminin-2 (Lm2, comprising the alpha2beta1gamma1 chains), as occurs in congenital muscular dystrophy, can lead to impaired oligodendroglial development and aberrant myelination, but many aspects of Lm2-regulated oligodendroglial signaling and differentiation remain undefined. We show that receptor-like protein tyrosine phosphatase alpha (PTPalpha, also known as PTPRA) is essential for myelin basic protein expression and cell spreading during Lm2-induced oligodendrocyte differentiation. PTPalpha complexes with the Lm2 receptors alpha6beta1 integrin and dystroglycan to transduce Fyn activation upon Lm2 engagement. In this way, PTPalpha mediates a subset of Lm2-induced signals required for differentiation, includeing mTOR-dependent Akt activation but not Erk1/2 activation. We identify N-myc downstream regulated gene-1 (NDRG1) as a PTPalpha-regulated molecule during oligodendrocyte differentiation, and distinguish Lm2 receptor-specific modes of Fyn-Akt-dependent and -independent NDRG1 phosphorylation. Altogether, this reveals an Lm2-regulated PTPalpha-Fyn-Akt signaling axis that is critical for key aspects of the gene expression and morphological changes that mark oligodendrocyte maturation. |
