Altered steady state and activity-dependent de novo protein expression in fragile X syndrome

Heather Bowling, Aditi Bhattacharya, Guoan Zhang, Danyal Alam, Joseph Z. Lebowitz, Nathaniel Bohm-Levine, Derek Lin, Priyangvada Singha, Maggie Mamcarz, Rosemary Puckett, Lili Zhou, Sameer Aryal, Kevin Sharp, Kent Kirshenbaum, Elizabeth Berry-Kravis, Thomas A. Neubert, Eric Klann

Research output: Contribution to journalArticle

Abstract

Whether fragile X mental retardation protein (FMRP) target mRNAs and neuronal activity contributing to elevated basal neuronal protein synthesis in fragile X syndrome (FXS) is unclear. Our proteomic experiments reveal that the de novo translational profile in FXS model mice is altered at steady state and in response to metabotropic glutamate receptor (mGluR) stimulation, but the proteins expressed differ under these conditions. Several altered proteins, including Hexokinase 1 and Ras, also are expressed in the blood of FXS model mice and pharmacological treatments previously reported to ameliorate phenotypes modify their abundance in blood. In addition, plasma levels of Hexokinase 1 and Ras differ between FXS patients and healthy volunteers. Our data suggest that brain-based de novo proteomics in FXS model mice can be used to find altered expression of proteins in blood that could serve as disease-state biomarkers in individuals with FXS.

Original languageEnglish (US)
Article number1710
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Fragile X Syndrome
proteins
Blood
blood
mice
Proteins
Fragile X Mental Retardation Protein
Proteomics
Metabotropic Glutamate Receptors
protein synthesis
Biomarkers
glutamates
phenotype
biomarkers
Brain
stimulation
brain
Blood Proteins
Healthy Volunteers
Plasmas

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Altered steady state and activity-dependent de novo protein expression in fragile X syndrome. / Bowling, Heather; Bhattacharya, Aditi; Zhang, Guoan; Alam, Danyal; Lebowitz, Joseph Z.; Bohm-Levine, Nathaniel; Lin, Derek; Singha, Priyangvada; Mamcarz, Maggie; Puckett, Rosemary; Zhou, Lili; Aryal, Sameer; Sharp, Kevin; Kirshenbaum, Kent; Berry-Kravis, Elizabeth; Neubert, Thomas A.; Klann, Eric.

In: Nature communications, Vol. 10, No. 1, 1710, 01.12.2019.

Research output: Contribution to journalArticle

Bowling, H, Bhattacharya, A, Zhang, G, Alam, D, Lebowitz, JZ, Bohm-Levine, N, Lin, D, Singha, P, Mamcarz, M, Puckett, R, Zhou, L, Aryal, S, Sharp, K, Kirshenbaum, K, Berry-Kravis, E, Neubert, TA & Klann, E 2019, 'Altered steady state and activity-dependent de novo protein expression in fragile X syndrome', Nature communications, vol. 10, no. 1, 1710. https://doi.org/10.1038/s41467-019-09553-8
Bowling H, Bhattacharya A, Zhang G, Alam D, Lebowitz JZ, Bohm-Levine N et al. Altered steady state and activity-dependent de novo protein expression in fragile X syndrome. Nature communications. 2019 Dec 1;10(1). 1710. https://doi.org/10.1038/s41467-019-09553-8
Bowling, Heather ; Bhattacharya, Aditi ; Zhang, Guoan ; Alam, Danyal ; Lebowitz, Joseph Z. ; Bohm-Levine, Nathaniel ; Lin, Derek ; Singha, Priyangvada ; Mamcarz, Maggie ; Puckett, Rosemary ; Zhou, Lili ; Aryal, Sameer ; Sharp, Kevin ; Kirshenbaum, Kent ; Berry-Kravis, Elizabeth ; Neubert, Thomas A. ; Klann, Eric. / Altered steady state and activity-dependent de novo protein expression in fragile X syndrome. In: Nature communications. 2019 ; Vol. 10, No. 1.
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