Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models

Autor: Zhong Ping Feng, Alexander J. Groffen, Ya Chi Huang, Hong Shuo Sun, Michael Wu, Jacqueline N. Crawley, Lucy R. Osborne, Ekaterina Turlova, Nardos G. Tassew, Wenliang Chen, Marielle Deurloo, You Wei Lin, Philippe P. Monnier, Elaine Tam
Přispěvatelé: Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Functional Genomics
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cortical neurons
Time Factors
Neurons/metabolism
TRPC3
Calcium in biology
Transcription Factors
TFII
Mice
0302 clinical medicine
Gene duplication
Williams-Beuren syndrome (WBS)
Neurons
General transcription factor
Phenotype
TRPC Cation Channels/metabolism
Cell biology
Transcription Factors
TFII/metabolism
Neurology
TFII/metabolism
Williams syndrome
Neurites/metabolism
congenital
hereditary
and neonatal diseases and abnormalities
Calcium/metabolism
Neuroscience (miscellaneous)
Context (language use)
Axons/metabolism
Biology
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
medicine
Neurites
Animals
Transcription factor
TRPC Cation Channels
Chromosome Aberrations
General transcription factor 2i
Animal
Cell Membrane/metabolism
Cell Membrane
medicine.disease
Axons
Disease Models
Animal
030104 developmental biology
Disease Models
Calcium
030217 neurology & neurosurgery
Transcription Factors
Zdroj: Molecular Neurobiology
Deurloo, M H S, Turlova, E, Chen, W-L, Lin, Y W, Tam, E, Tassew, N G, Wu, M, Huang, Y-C, Crawley, J N, Monnier, P P, Groffen, A J A, Sun, H-S, Osborne, L R & Feng, Z-P 2019, ' Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models ', Molecular Neurobiology, vol. 56, no. 5, pp. 3313-3325 . https://doi.org/10.1007/s12035-018-1290-7
Molecular Neurobiology, 56(5), 3313-3325. Humana Press
Deurloo, M H S, Turlova, E, Chen, W L, Lin, Y W, Tam, E, Tassew, N G, Wu, M, Huang, Y C, Crawley, J N, Monnier, P P, Groffen, A J A, Sun, H S, Osborne, L R & Feng, Z P 2019, ' Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models ', Molecular Neurobiology, vol. 56, no. 5, pp. 3313-3325 . https://doi.org/10.1007/s12035-018-1290-7
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-018-1290-7
Popis: Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are neurodevelopmental disorders caused by the deletion and duplication, respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here, we investigated the effect of copy number alterations in Gtf2i on neuronal maturation and intracellular calcium entry mechanisms known to be associated with this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation. In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane translocation. Together, our results provide novel functional insight into the cellular mechanisms that underlie neuronal maturation in the context of the 7q11.23 disorders. Electronic supplementary material The online version of this article (10.1007/s12035-018-1290-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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