Increased expression of the PI3K catalytic subunit p110δ underlies elevated S6 phosphorylation and protein synthesis in an individual with autism from a multiplex family

Molecular Autism
Ashwini C PoopalChristina Gross

Abstract

Dysfunctions in the PI3K/mTOR pathway have gained a lot of attention in autism research. This was initially based on the discovery of several monogenic autism spectrum disorders with mutations or defects in PI3K/mTOR signaling components. Recent genetic studies corroborate that defective PI3K/mTOR signaling might be a shared pathomechanism in autism disorders of so far unknown etiology, but functional molecular analyses in human cells are rare. The goals of this study were to perform a functional screen of cell lines from patients with idiopathic autism for defects in PI3K/mTOR signaling, to test if further functional analyses are suitable to detect underlying molecular mechanisms, and to evaluate this approach as a biomarker tool to identify therapeutic targets. We performed phospho-S6- and S6-specific ELISA experiments on 21 lymphoblastoid cell lines from the AGRE collection and on 37 lymphoblastoid cell lines from the Simons Simplex Collection and their healthy siblings. Cell lines from one individual with increased S6 phosphorylation and his multiplex family were analyzed in further detail to identify upstream defects in PI3K signaling associated with autism diagnosis. We detected significantly increased S6 phosphorylation ...Continue Reading

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Citations

Mar 25, 2017·International Journal of Molecular Sciences·Juliana MagdalonAndréa L Sertié
Feb 2, 2019·Translational Psychiatry·Eleonora RosinaClaudia Bagni
Jun 19, 2019·Human Molecular Genetics·Veronica L HoodAmanda J Law
Mar 11, 2020·Autism Research : Official Journal of the International Society for Autism Research·Milena CioanaMargaret Fahnestock
Jul 5, 2016·Journal of Neuroscience Research·Christina Gross
Jun 16, 2018·F1000Research·Fatma Ayhan, Genevieve Konopka
Mar 18, 2020·Frontiers in Molecular Neuroscience·Veronica L HoodAmanda J Law
May 18, 2021·Biochemistry. Biokhimii︠a︡·Irina S BokshaGulnur Sh Burbaeva

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Methods Mentioned

BETA
immunoprecipitation
ELISA
ELISAs

Software Mentioned

GraphPad Prism
ImageJ
SAS®
GraphPad

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