The role of calcium-dependent gene expression in autism spectrum disorders: lessons from MeCP2, Ube3a and beyond.
During the last decade, autism spectrum disorders (ASD) have become the center of attention where several branches of modern biology unexpectedly meet, such as neural development, molecular biology, epigenetics, neurophysiology and psychiatry. This review will focus on the molecular mechanism by which calcium-dependent gene expression regulates brain development and how ASD may occur if this process is compromised. Specifically, the studies of the calcium-dependent transcriptional repressor MeCP2 gave us much insight about how abnormal development may lead to ASD. Most recently, studies about Ube3a, a critical component of the ubiquitination system enzyme, shed light on how neural activity regulates synapse function through the protein degradation pathway. Taken together, these studies suggest that ASD may be caused by the incapability of neurons to generate adaptive responses via regulating gene expression upon incoming activity.
Qiu
Zilong
Z
Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China. zqiu@ion.ac.cn
Cheng
Ju
J
D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D008967:Molecular Biology; D015518:Rett Syndrome / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*
D051783:Methyl-CpG-Binding Protein 2; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases