RNA-sequencing of Zdhhc5 knockout oligodendrocytes

Myelin sheath is an important structure to maintain normal functions of the nerves in central nervous system. Protein palmitoylation has been established as a sorting determinant for the transport of myelin-forming proteins to the myelin membrane. However, its function in the regulation of oligodendrocyte development remains unknown. Here, we show that an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC5, is involved in the control of oligodendrocyte development. Loss of Zdhhc5 in oligodendrocytes inhibits myelination and remyelination by a reduction on total myelinating oligodendrocyte population. STAT3 is the primary substrate for DHHC5 palmitoylation in oligodendrocytes. Zdhhc5 ablation reduces STAT3 palmitoylation, and then suppresses STAT3 phosphorylation and activation. As a result of the decreased STAT3 transactivity, the transcription of the myelin-related and anti-apoptosis genes is therefore inhibited, leading to suppressed oligodendrocyte development and myelination. Our findings demonstrate the key role DHHC5 in the control of myelinogenesis. Overall design: Comparison of mRNA profiles of wild type (WT) and Zdhhc5 knockout oligodendrocytes.