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

Marielle H.S. Deurloo, Ekaterina Turlova, Wen Liang Chen, You Wei Lin, Elaine Tam, Nardos G. Tassew, Michael Wu, Ya Chi Huang, Jacqueline N. Crawley, Philippe P. Monnier, Alexander J.A. Groffen, Hong Shuo Sun, Lucy R. Osborne, Zhong Ping Feng

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMolecular Neurobiology
DOIs
Publication statusE-pub ahead of print - 17 Aug 2018

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Transcription Factors
Williams Syndrome
Calcium
Proteins
General Transcription Factors
Carbachol
Chromosomes
Phenotype
Membranes

Keywords

  • Cortical neurons
  • General transcription factor 2i
  • TRPC3
  • Williams-Beuren syndrome (WBS)

Cite this

Deurloo, M. H. S., Turlova, E., Chen, W. L., Lin, Y. W., Tam, E., Tassew, N. G., ... Feng, Z. P. (2018). Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models. Molecular Neurobiology, 1-13. https://doi.org/10.1007/s12035-018-1290-7
Deurloo, Marielle H.S. ; Turlova, Ekaterina ; Chen, Wen Liang ; Lin, You Wei ; Tam, Elaine ; Tassew, Nardos G. ; Wu, Michael ; Huang, Ya Chi ; Crawley, Jacqueline N. ; Monnier, Philippe P. ; Groffen, Alexander J.A. ; Sun, Hong Shuo ; Osborne, Lucy R. ; Feng, Zhong Ping. / Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models. In: Molecular Neurobiology. 2018 ; pp. 1-13.
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abstract = "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.",
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author = "Deurloo, {Marielle H.S.} and Ekaterina Turlova and Chen, {Wen Liang} and Lin, {You Wei} and Elaine Tam and Tassew, {Nardos G.} and Michael Wu and Huang, {Ya Chi} and Crawley, {Jacqueline N.} and Monnier, {Philippe P.} and Groffen, {Alexander J.A.} and Sun, {Hong Shuo} and Osborne, {Lucy R.} and Feng, {Zhong Ping}",
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Deurloo, MHS, Turlova, E, Chen, WL, Lin, YW, Tam, E, Tassew, NG, Wu, M, Huang, YC, Crawley, JN, Monnier, PP, Groffen, AJA, Sun, HS, Osborne, LR & Feng, ZP 2018, 'Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models' Molecular Neurobiology, pp. 1-13. https://doi.org/10.1007/s12035-018-1290-7

Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models. / Deurloo, Marielle H.S.; Turlova, Ekaterina; Chen, Wen Liang; Lin, You Wei; Tam, Elaine; Tassew, Nardos G.; Wu, Michael; Huang, Ya Chi; Crawley, Jacqueline N.; Monnier, Philippe P.; Groffen, Alexander J.A.; Sun, Hong Shuo; Osborne, Lucy R.; Feng, Zhong Ping.

In: Molecular Neurobiology, 17.08.2018, p. 1-13.

Research output: Contribution to JournalArticleAcademicpeer-review

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T1 - Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23 Disorder Models

AU - Deurloo, Marielle H.S.

AU - Turlova, Ekaterina

AU - Chen, Wen Liang

AU - Lin, You Wei

AU - Tam, Elaine

AU - Tassew, Nardos G.

AU - Wu, Michael

AU - Huang, Ya Chi

AU - Crawley, Jacqueline N.

AU - Monnier, Philippe P.

AU - Groffen, Alexander J.A.

AU - Sun, Hong Shuo

AU - Osborne, Lucy R.

AU - Feng, Zhong Ping

PY - 2018/8/17

Y1 - 2018/8/17

N2 - 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.

AB - 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.

KW - Cortical neurons

KW - General transcription factor 2i

KW - TRPC3

KW - Williams-Beuren syndrome (WBS)

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