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Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice
Adhesion molecules regulate cell proliferation, migration, survival, neuritogenesis, synapse formation and synaptic plasticity during the nervous system’s development and in the adult. Among such molecules, the neural cell adhesion molecule L1 contributes to these functions during development, and i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026747/ https://www.ncbi.nlm.nih.gov/pubmed/35457156 http://dx.doi.org/10.3390/ijms23084337 |
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author | Congiu, Ludovica Granato, Viviana Loers, Gabriele Kleene, Ralf Schachner, Melitta |
author_facet | Congiu, Ludovica Granato, Viviana Loers, Gabriele Kleene, Ralf Schachner, Melitta |
author_sort | Congiu, Ludovica |
collection | PubMed |
description | Adhesion molecules regulate cell proliferation, migration, survival, neuritogenesis, synapse formation and synaptic plasticity during the nervous system’s development and in the adult. Among such molecules, the neural cell adhesion molecule L1 contributes to these functions during development, and in synapse formation, synaptic plasticity and regeneration after trauma. Proteolytic cleavage of L1 by different proteases is essential for these functions. A proteolytic fragment of 70 kDa (abbreviated L1-70) comprising part of the extracellular domain and the transmembrane and intracellular domains was shown to interact with mitochondrial proteins and is suggested to be involved in mitochondrial functions. To further determine the role of L1-70 in mitochondria, we generated two lines of gene-edited mice expressing full-length L1, but no or only low levels of L1-70. We showed that in the absence of L1-70, mitochondria in cultured cerebellar neurons move more retrogradely and exhibit reduced mitochondrial membrane potential, impaired Complex I activity and lower ATP levels compared to wild-type littermates. Neither neuronal migration, neuronal survival nor neuritogenesis in these mutants were stimulated with a function-triggering L1 antibody or with small agonistic L1 mimetics. These results suggest that L1-70 is important for mitochondrial homeostasis and that its absence contributes to the L1 syndrome phenotypes. |
format | Online Article Text |
id | pubmed-9026747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90267472022-04-23 Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice Congiu, Ludovica Granato, Viviana Loers, Gabriele Kleene, Ralf Schachner, Melitta Int J Mol Sci Article Adhesion molecules regulate cell proliferation, migration, survival, neuritogenesis, synapse formation and synaptic plasticity during the nervous system’s development and in the adult. Among such molecules, the neural cell adhesion molecule L1 contributes to these functions during development, and in synapse formation, synaptic plasticity and regeneration after trauma. Proteolytic cleavage of L1 by different proteases is essential for these functions. A proteolytic fragment of 70 kDa (abbreviated L1-70) comprising part of the extracellular domain and the transmembrane and intracellular domains was shown to interact with mitochondrial proteins and is suggested to be involved in mitochondrial functions. To further determine the role of L1-70 in mitochondria, we generated two lines of gene-edited mice expressing full-length L1, but no or only low levels of L1-70. We showed that in the absence of L1-70, mitochondria in cultured cerebellar neurons move more retrogradely and exhibit reduced mitochondrial membrane potential, impaired Complex I activity and lower ATP levels compared to wild-type littermates. Neither neuronal migration, neuronal survival nor neuritogenesis in these mutants were stimulated with a function-triggering L1 antibody or with small agonistic L1 mimetics. These results suggest that L1-70 is important for mitochondrial homeostasis and that its absence contributes to the L1 syndrome phenotypes. MDPI 2022-04-14 /pmc/articles/PMC9026747/ /pubmed/35457156 http://dx.doi.org/10.3390/ijms23084337 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Congiu, Ludovica Granato, Viviana Loers, Gabriele Kleene, Ralf Schachner, Melitta Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice |
title | Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice |
title_full | Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice |
title_fullStr | Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice |
title_full_unstemmed | Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice |
title_short | Mitochondrial and Neuronal Dysfunctions in L1 Mutant Mice |
title_sort | mitochondrial and neuronal dysfunctions in l1 mutant mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026747/ https://www.ncbi.nlm.nih.gov/pubmed/35457156 http://dx.doi.org/10.3390/ijms23084337 |
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