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

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 nervo...

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Autores principales: Zhang, Albert, Ackley, Brian D., Yan, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281833/
https://www.ncbi.nlm.nih.gov/pubmed/32209461
http://dx.doi.org/10.1016/j.celrep.2020.02.113
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author Zhang, Albert
Ackley, Brian D.
Yan, Dong
author_facet Zhang, Albert
Ackley, Brian D.
Yan, Dong
author_sort Zhang, Albert
collection PubMed
description 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.
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spelling pubmed-72818332020-06-09 Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression Zhang, Albert Ackley, Brian D. Yan, Dong Cell Rep Article 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. 2020-03-24 /pmc/articles/PMC7281833/ /pubmed/32209461 http://dx.doi.org/10.1016/j.celrep.2020.02.113 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhang, Albert
Ackley, Brian D.
Yan, Dong
Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression
title Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression
title_full Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression
title_fullStr Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression
title_full_unstemmed Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression
title_short Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression
title_sort vitamin b12 regulates glial migration and synapse formation through isoform-specific control of ptp-3/lar prtp expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281833/
https://www.ncbi.nlm.nih.gov/pubmed/32209461
http://dx.doi.org/10.1016/j.celrep.2020.02.113
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