Quantitative profiling of brain lipid raft proteome in a mouse model of Fragile X syndrome

Magdalena Kalinowska, Catherine Castillo, Anna Francesconi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Fragile X Syndrome, a leading cause of inherited intellectual disability and autism, arises from transcriptional silencing of the FMR1 gene encoding an RNA-binding protein, Fragile X Mental Retardation Protein (FMRP). FMRP can regulate the expression of approximately 4% of brain transcripts through its role in regulation of mRNA transport, stability and translation, thus providing a molecular rationale for its potential pleiotropic effects on neuronal and brain circuitry function. Several intracellular signaling pathways are dysregulated in the absence of FMRP suggesting that cellular deficits may be broad and could result in homeostatic changes. Lipid rafts are specialized regions of the plasma membrane, enriched in cholesterol and glycosphingolipids, involved in regulation of intracellular signaling. Among transcripts targeted by FMRP, a subset encodes proteins involved in lipid biosynthesis and homeostasis, dysregulation of which could affect the integrity and function of lipid rafts. Using a quantitative mass spectrometry-based approach we analyzed the lipid raft proteome of Fmr1 knockout mice, an animal model of Fragile X syndrome, and identified candidate proteins that are differentially represented in Fmr1 knockout mice lipid rafts. Furthermore, network analysis of these candidate proteins reveals connectivity between them and predicts functional connectivity with genes encoding components of myelin sheath, axonal processes and growth cones. Our findings provide insight to aid identification of molecular and cellular dysfunctions arising from Fmr1 silencing and for uncovering shared pathologies between Fragile X syndrome and other autism spectrum disorders.

Original languageEnglish (US)
Article numbere121464
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 7 2015

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Fragile X Syndrome
Fragile X Mental Retardation Protein
Proteome
proteome
Brain
animal models
brain
Lipids
lipids
Gene encoding
proteins
Knockout Mice
Gene Components
Glycosphingolipids
Growth Cones
Proteins
RNA-Binding Proteins
Biosynthesis
RNA Stability
Protein Biosynthesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Quantitative profiling of brain lipid raft proteome in a mouse model of Fragile X syndrome. / Kalinowska, Magdalena; Castillo, Catherine; Francesconi, Anna.

In: PLoS One, Vol. 10, No. 4, e121464, 07.04.2015.

Research output: Contribution to journalArticle

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