PT  - JOURNAL ARTICLE
AU  - Alexandra Alves-Sampaio
AU  - José Antonio Troca-Marín
AU  - María Luz Montesinos
TI  - NMDA-Mediated Regulation of <em>DSCAM</em> Dendritic Local Translation Is Lost in a Mouse Model of Down's Syndrome
AID  - 10.1523/JNEUROSCI.3457-10.2010
DP  - 2010 Oct 06
TA  - The Journal of Neuroscience
PG  - 13537--13548
VI  - 30
IP  - 40
4099  - http://www.jneurosci.org/content/30/40/13537.short
4100  - http://www.jneurosci.org/content/30/40/13537.full
SO  - J. Neurosci.2010 Oct 06; 30
AB  - Down's syndrome cell adhesion molecule (DSCAM) belongs to the Down's syndrome critical region of human chromosome 21, and it encodes a cell adhesion molecule involved in dendrite morphology and neuronal wiring. Although the function of DSCAM in the adult brain is unknown, its expression pattern suggests a role in synaptic plasticity. Local mRNA translation is a key process in axonal growth, dendritogenesis, and synaptogenesis during development, and in synaptic plasticity in adulthood. Here, we report the dendritic localization of DSCAM mRNA in the adult mouse hippocampus, where it associates with CPEB1 [cytoplasmic polyadenylation element (CPE) binding protein 1], an important regulator of mRNA transport and local translation. We identified five DSCAM isoforms produced by alternative polyadenylation bearing different combinations of regulatory CPE motifs. Overexpression of DSCAM in hippocampal neurons inhibited dendritic branching. Interestingly, dendritic levels of DSCAM mRNA and protein were increased in hippocampal neurons from Ts1Cje mice, a model of Down's syndrome. Most importantly, DSCAM dendritic translation was rapidly induced by NMDA in wild-type, but not in Ts1Cje neurons. We propose that impairment of the NMDA-mediated regulation of DSCAM translation may contribute to the alterations in dendritic morphology and/or synaptic plasticity in Down's syndrome.