title: JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse.
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.
authors.affiliation: Interdepartmental Program for Neuroscience, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jamee M
authors.initials: JM
authors.lastname: Berg
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Lee
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Galvan
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Peñagarikano
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Stein
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Alvin
authors.initials: A
authors.lastname: Li
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Asami
authors.initials: A
authors.lastname: Oguro-Ando
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Starks
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Elyse P
authors.initials: EP
authors.lastname: Kite
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Tam
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Amos
authors.initials: A
authors.lastname: Gdalyahu
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Noor B
authors.initials: NB
authors.lastname: Al-Sharif
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Interdepartmental Program in Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Burkett
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Interdepartmental Program in Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: White
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Fears
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA; Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism*; D053263:Gene Regulatory Networks / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*; D040901:Proteomics / Q000379:methods; D016601:RNA-Binding Proteins / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C484851:JAKMIP1 protein, human; D016601:RNA-Binding Proteins