Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression

• Published in: Cell reports (Cambridge) Vol. 30; no. 12; pp. 3981 - 3988.e3
• Main Authors: Zhang, Albert, Ackley, Brian D., Yan, Dong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.03.2020; Elsevier
• Subjects: Animals; C. elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - enzymology; Caenorhabditis elegans Proteins - metabolism; Cell Movement - drug effects; glial development; glial migration; Neuroglia - cytology; Neuroglia - drug effects; neuronal development; Protein Isoforms - metabolism; Protein Tyrosine Phosphatases - metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - metabolism; synapse formation; Synapses - drug effects; Synapses - metabolism; Vitamin B 12 - pharmacology; vitamin B12; neuronal development; glial migration; C. elegans; vitamin B12; glial development; synapse formation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.02.113

Vitamin B12 is known to play critical roles during the development and aging of the brain, and vitamin B12 deficiency has been linked to neurodevelopmental and degenerative disorders. However, the underlying molecular mechanisms of how vitamin B12 affects the development and maintenance of the nervous system are still unclear. Here, we report that vitamin B12 can regulate glial migration and synapse formation through control of isoform-specific expression of PTP-3/LAR PRTP (leukocyte-common antigen-related receptor-type tyrosine-protein phosphatase). We found the uptake of diet-supplied vitamin B12 in the intestine to be critical for the expression of a long isoform of PTP-3 (PTP-3A) in neuronal and glial cells. The expression of PTP-3A cell autonomously regulates glial migration and synapse formation through interaction with an extracellular matrix protein NID-1/nidogen 1. Together, our findings demonstrate that isoform-specific regulation of PTP-3/ LAR PRTP expression is a key molecular mechanism that mediates vitamin-B12-dependent neuronal and glial development. [Display omitted] •Vitamin B12 plays a role in regulating glial migration through PTP-3/LAR PRTP•PTP-3 functions cell autonomously in an isoform-specific manner•Vitamin B12 deficiency leads disruption of synapse formation•PTP-3 functions by interacting with the extracellular matrix protein NID-1 Zhang et al. describe glial migration and synapse formation defects stemming from vitamin B12 deficiency. Their study identifies a cell-autonomous mechanism regulating glial migration, where vitamin B12 regulates expression of the cell adhesion molecule PTP-3/LAR PRTP in an isoform-specific manner.