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Wiring up the newest part of the cortex.

Choi CQ - PLoS Biol. (2012)

View Article: PubMed Central - PubMed

Affiliation: cqchoi@sciwriter.us

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There are two types of dendrites defined by location: apical dendrites, which stretch far from the cell bodies toward the surface of the brain, and basal dendrites found close to the cell bodies... The scientists focused on a protein called Epac2, which helps regulate Rap, a Ras-like small GTPase highly enriched in the adult brain and dendrites... By knocking down Epac2 in a specific population of pyramidal neurons in the mouse cortex, they found that this led to a significant reduction in both the number and length of basal dendritic branches... Interestingly, four rare amino acid coding variants have been identified in the EPAC2 gene in people with autism, suggesting they could help yield insights on the protein's function... Therefore, the authors overexpressed one of these mutant proteins in cultured rat cortical neurons, and again found reduced basal dendritic complexity and length... This single amino-acid mutation, seen in four people with autism from two families, is located within the Ras association domain of Epac2... The authors tested this by first showing that Epac2 normally interacted with Ras in cultured rat cortical neurons, but that the mutant Epac2 had significantly impaired interactions with Ras... Importantly, disrupting Ras pharmacologically in cultured neurons also reduced basal dendritic complexity and length... Penzes and his colleagues conclude that Epac2 enables crosstalk between the Ras and Rap signaling pathways to maintain basal dendrite complexity... When they looked at the expression of these proteins in different regions of pyramidal neurons, they found that each protein was less concentrated in basal dendrites than apical ones, which suggests that these lower levels of Epac2, Ras, and Rap could make basal dendrites more vulnerable to impairments such as mutations... It may be that Epac2 is part of a signaling network, as Penzes and his colleagues have previously shown that Epac2 interacts with neuroligins, important autism susceptibility molecules.

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Apical and basal dendrites of cortical pyramidal neurons exhibit distinct shapes, and basal dendrites retract when Ras-Epac2 signaling is disrupted.
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pbio-1001355-g001: Apical and basal dendrites of cortical pyramidal neurons exhibit distinct shapes, and basal dendrites retract when Ras-Epac2 signaling is disrupted.


Wiring up the newest part of the cortex.

Choi CQ - PLoS Biol. (2012)

Apical and basal dendrites of cortical pyramidal neurons exhibit distinct shapes, and basal dendrites retract when Ras-Epac2 signaling is disrupted.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3383731&req=5

pbio-1001355-g001: Apical and basal dendrites of cortical pyramidal neurons exhibit distinct shapes, and basal dendrites retract when Ras-Epac2 signaling is disrupted.

View Article: PubMed Central - PubMed

Affiliation: cqchoi@sciwriter.us

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

There are two types of dendrites defined by location: apical dendrites, which stretch far from the cell bodies toward the surface of the brain, and basal dendrites found close to the cell bodies... The scientists focused on a protein called Epac2, which helps regulate Rap, a Ras-like small GTPase highly enriched in the adult brain and dendrites... By knocking down Epac2 in a specific population of pyramidal neurons in the mouse cortex, they found that this led to a significant reduction in both the number and length of basal dendritic branches... Interestingly, four rare amino acid coding variants have been identified in the EPAC2 gene in people with autism, suggesting they could help yield insights on the protein's function... Therefore, the authors overexpressed one of these mutant proteins in cultured rat cortical neurons, and again found reduced basal dendritic complexity and length... This single amino-acid mutation, seen in four people with autism from two families, is located within the Ras association domain of Epac2... The authors tested this by first showing that Epac2 normally interacted with Ras in cultured rat cortical neurons, but that the mutant Epac2 had significantly impaired interactions with Ras... Importantly, disrupting Ras pharmacologically in cultured neurons also reduced basal dendritic complexity and length... Penzes and his colleagues conclude that Epac2 enables crosstalk between the Ras and Rap signaling pathways to maintain basal dendrite complexity... When they looked at the expression of these proteins in different regions of pyramidal neurons, they found that each protein was less concentrated in basal dendrites than apical ones, which suggests that these lower levels of Epac2, Ras, and Rap could make basal dendrites more vulnerable to impairments such as mutations... It may be that Epac2 is part of a signaling network, as Penzes and his colleagues have previously shown that Epac2 interacts with neuroligins, important autism susceptibility molecules.

Show MeSH