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- Title
LINGO-1 Regulates Oligodendrocyte Differentiation through the Cytoplasmic Gelsolin Signaling Pathway.
- Authors
Zhaohui Shao; Xinhua Lee; Guanrong Huang; Guoqing Sheng; Henderson, Christopher E.; Louvard, Daniel; Jiho Sohn; Pepinsky, Blake; Sha Mi
- Abstract
Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. However, how actin dynamics are regulated during this process remains poorly understood. Leucine-rich repeat and Ig-like domain-containing Nogo receptor interacting protein 1 (LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody-promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments. Treating rat OPCs with cGSN siRNA reduced OPC differentiation, whereas overexpression of cGSN promoted OPC differentiation in vitro and remyelination in vivo. Furthermore, coexpression of cGSN and LINGO-1 blocked the inhibitory effect of LINGO-1. Our study demonstrates that cGSN works downstream of LINGO-1 signaling pathway, which enhances actin dynamics and is essential for OPC morphogenesis and differentiation. This finding may lead to novel therapeutic approaches for the treatment of demyelinating diseases such as multiple sclerosis (MS).
- Subjects
DEMYELINATION; OLIGODENDROGLIA; CELL differentiation; NOGO receptors; GELSOLIN; CELLULAR signal transduction; MULTIPLE sclerosis treatment; GENETIC overexpression; PHYSIOLOGY; THERAPEUTICS
- Publication
Journal of Neuroscience, 2017, Vol 37, Issue 12, p3127
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3722-16.2017