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

Cell Rep. 2020 Mar 24;30(12):3981-3988.e3. 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.

Keywords: C. elegans; glial development; glial migration; neuronal development; synapse formation; vitamin B12.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Movement* / drug effects
  • Neuroglia / cytology*
  • Neuroglia / drug effects
  • Protein Isoforms / metabolism
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism*
  • Vitamin B 12 / pharmacology*


  • Caenorhabditis elegans Proteins
  • Protein Isoforms
  • PTP-3 protein, C elegans
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Vitamin B 12