title: Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders.
abstract: Autism spectrum disorder (ASD) is a heterogeneous group of heritable neurodevelopmental disorders. Symptoms of ASD, which include deficits in social interaction skills, impaired communication ability, and ritualistic-like repetitive behaviors, appear in early childhood and continue throughout life. Genetic studies have revealed at least two clusters of genes frequently associated with ASD and intellectual disability: those encoding proteins involved in translational control and those encoding proteins involved in synaptic function. We hypothesize that mutations occurring in these two clusters of genes interfere with interconnected downstream signaling pathways in neuronal cells to cause ASD symptomatology. In this review, we discuss the monogenic forms of ASD caused by mutations in genes encoding for proteins that regulate translation and synaptic function. Specifically, we describe the function of these proteins, the intracellular signaling pathways that they regulate, and the current mouse models used to characterize the synaptic and behavioral features associated with their mutation. Finally, we summarize recent studies that have established a connection between mRNA translation and synaptic function in models of ASD and propose that dysregulation of one has a detrimental impact on the other.
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Santini
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003, USA. ek65@nyu.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Klann
mesh_terms: D000818:Animals; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000503:physiopathology*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics* / Q000502:physiology; D000074407:SAP90-PSD95 Associated Proteins; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D051059:PTEN Phosphohydrolase; D000074407:SAP90-PSD95 Associated Proteins; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020703:ras GTPase-Activating Proteins; C122162:SHANK2 protein, human; C484739:SYNGAP1 protein, human; C494929:PTEN protein, human