JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse
نویسندگان
چکیده
Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. Here, we provide multiple lines of evidence that JAKMIP1 is a component of polyribosomes and an RNP translational regulatory complex that includes fragile X mental retardation protein, DEAD box helicase 5, and the poly(A) binding protein cytoplasmic 1. JAKMIP1 loss dysregulates neuronal translation during synaptic development, affecting glutamatergic NMDAR signaling, and results in social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors in the mouse. These findings define an important and novel role for JAKMIP1 in neural development and further highlight pathways regulating mRNA translation during synaptogenesis in the genesis of neurodevelopmental disorders.
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In this issue of Neuron, Berg et al. (2015) uncover multifaceted roles for janus kinase and microtubule-interacting protein 1 (JAKMIP1) in regulating neuronal mRNA translation and establish JAKMIP1 knockout mice as an important model to study autism spectrum disorder-associated phenotypes.
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ورودعنوان ژورنال:
- Neuron
دوره 88 شماره
صفحات -
تاریخ انتشار 2015