Myelin sheaths are generated from differentiated plasma membranes of oligodendroglial cells (oligodendrocytes) during development. Despite detailed functional studies, such as aiding nerve conduction velocity, it remains unclear which extracellular signals from neurons interact with oligodendrocytes to control oligodendrocyte development and how these are achieved. Herein, we demonstrate that the Plexin molecule Plexin-B3, generally known as a receptor for Sema family signaling proteins, is specifically expressed in oligodendrocytes and plays a key role in promoting oligodendrocyte maturation and myelination. Oligodendrocyte-specific conditional male knock-out mice of Plexin-B3 exhibited decreased myelin thickness and myelin marker protein expression, compared with littermate controls. Unexpectedly, we identified heat shock protein family A member 5 (HSPA5)/Grp78/BiP as the neuron-secreted ligand of Plexin-B3. Indeed, neuron-specific knockdown of HSPA5 in male mice revealed a critical role for myelin thickness not only at the biochemical level but also at the histochemical one. Furthermore, the transcription factor Nkx2.8, which plays a role in oligodendrocytes, was identified as a potential mediator of Plexin-B3 signaling. Our results suggest that the interaction of extracellular HSPA5 with Plexin-B3 on oligodendrocytes, acting possibly through Nkx2.8, regulates oligodendrocyte maturation and myelination. This ligand and receptor interaction and a downstream molecule are newly added to the list of emerging signaling units controlling myelination.
To facilitate access to relevant text of literature related to data in GlyCosmos, we have developed a collection of annotated literature resources using the agile annotation method supported by the PubAnnotation system. As a proof of concept, we compiled two dictionaries for glycan motifs and epitopes, plus six additional dictionaries for relevant biological entities, covering organisms, phenotypes, diseases, and anatomical locations. Next, we collected all the PubMed abstracts from 15 selected journals, and annotated them based on these eight dictionaries. This resulted in 279,368 annotation instances made to 15,463 abstracts, meaning that we were able to automatically pull glycan motif and epitope annotations related to diseases, taxonomy, etc. from over 15,000 abstracts. All the annotations were converted into Resource Description Framework (RDF) statements to support flexible querying. For users who are not familiar with RDF, we also developed a Web interface in GlyCosmos to visualize the location of the text in publications as well as query templates to personalize queries for specific terms. Pilot searches and analyses suggest that these resources are useful for navigation of relevant contexts of biomedical associations relevant to glycobiology.
