JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse

Jamee M. Berg, Changhoon Lee, Leslie Chen, Laurie Galvan, Carlos Cepeda, Jane Y. Chen, Olga Peñagarikano, Jason L. Stein, Alvin Li, Asami Oguro-Ando, Jeremy A. Miller, Ajay A. Vashisht, Mary E. Starks, Elyse P. Kite, Eric Tam, Amos Gdalyahu, Noor B. Al-Sharif, Zachary D. Burkett, Stephanie A. White, Scott C. FearsMichael S. Levine, James A. Wohlschlegel, Daniel H. Geschwind

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1173-1191
Number of pages19
JournalNeuron
Volume88
Issue number6
DOIs
StatePublished - 2015
Externally publishedYes

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