TY - JOUR
T1 - Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders
AU - Santini, Emanuela
AU - Klann, Eric
N1 - Publisher Copyright:
Copyright © 2014 American Association for the Advancement of Science. All Rights Reserved.
PY - 2014/10/28
Y1 - 2014/10/28
N2 - 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.
AB - 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.
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U2 - 10.1126/scisignal.2005832
DO - 10.1126/scisignal.2005832
M3 - Review article
C2 - 25351249
AN - SCOPUS:84908587395
SN - 1945-0877
VL - 7
JO - Science signaling
JF - Science signaling
IS - 349
M1 - 2005832
ER -