@article{8a3b52401301465eb378fe1e5cf49ec8,
title = "Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons",
abstract = "L-type voltage gated calcium channels have an important role in neuronal development by promoting dendritic growth and arborization. A point mutation in the gene encoding Ca V 1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs). We report that channels with the Timothy syndrome alteration cause activity-dependent dendrite retraction in rat and mouse neurons and in induced pluripotent stem cell (iPSC)-derived neurons from individuals with Timothy syndrome. Dendrite retraction was independent of calcium permeation through the mutant channel, was associated with ectopic activation of RhoA and was inhibited by overexpression of the channel-associated GTPase Gem. These results suggest that Ca V 1.2 can activate RhoA signaling independently of Ca2+ and provide insights into the cellular basis of Timothy syndrome and other ASDs.",
author = "Krey, {Jocelyn F.} and Pa{\c s}ca, {Sergiu P.} and Aleksandr Shcheglovitov and Masayuki Yazawa and Rachel Schwemberger and Randall Rasmusson and Dolmetsch, {Ricardo E.}",
note = "Funding Information: We thank K. Timothy and the individuals with Timothy syndrome who participated in this study, J. Bernstein and J. Hallmayer for recruiting the subjects for this study, and E. Nigh for critical reading of the manuscript. J.F.K. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award (F31 NS055549-03) from the National Institute of Neurological Disorders and Stroke. Financial support was provided by a US National Institutes of Health Director{\textquoteright}s Pioneer Award and a Simons Foundation Grant to R.E.D.; the International Brain Research Organization Outstanding Research Fellowship and the Tashia and John Morgridge Endowed Fellowship to S.P.P.; a Japan Society of the Promotion for Science Postdoctoral Fellowship for Research Abroad and American Heart Association Western States to M.Y.; and a California Institute for Regenerative Medicine Postdoctoral Fellowship to O.S. We are grateful for funding from B. and F. Horowitz, M. McCafferey, B. and J. Packard, P. Kwan and K. Wang.",
year = "2013",
month = feb,
doi = "10.1038/nn.3307",
language = "English (US)",
volume = "16",
pages = "201--209",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "2",
}