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Am J Pathol. 2011 Jul;179(1):66-74. doi: 10.1016/j.ajpath.2011.03.034. Epub 2011 May 7.

Abnormal cell properties and down-regulated FAK-Src complex signaling in B lymphoblasts of autistic subjects.

Author information

1
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, New York, New York 10314, USA.

Erratum in

  • Am J Pathol. 2011 Nov;179(5):2674.

Abstract

Recent studies suggest that one of the major pathways to the pathogenesis of autism is reduced cell migration. Focal adhesion kinase (FAK) has an important role in neural migration, dendritic morphological characteristics, axonal branching, and synapse formation. The FAK-Src complex, activated by upstream reelin and integrin β1, can initiate a cascade of phosphorylation events to trigger multiple intracellular pathways, including mitogen-activated protein kinase-extracellular signal-regulated kinase and phosphatidylinositol 3-kinase-Akt signaling. In this study, by using B lymphoblasts as a model, we tested whether integrin β1 and FAK-Src signaling are abnormally regulated in autism and whether abnormal FAK-Src signaling leads to defects in B-lymphoblast adhesion, migration, proliferation, and IgG production. To our knowledge, for the first time, we show that protein expression levels of both integrin β1 and FAK are significantly decreased in autistic lymphoblasts and that Src protein expression and the phosphorylation of an active site (Y416) are also significantly decreased. We also found that lymphoblasts from autistic subjects exhibit significantly decreased migration, increased adhesion properties, and an impaired capacity for IgG production. The overexpression of FAK in autistic lymphoblasts countered the adhesion and migration defects. In addition, we demonstrate that FAK mediates its effect through the activation of Src, phosphatidylinositol 3-kinase-Akt, and mitogen-activated protein kinase signaling cascades and that paxillin is also likely involved in the regulation of adhesion and migration in autistic lymphoblasts.

PMID:
21703394
PMCID:
PMC3123809
DOI:
10.1016/j.ajpath.2011.03.034
[Indexed for MEDLINE]
Free PMC Article

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