@article{eb6e6c1a41a6473bbcc028bb429df95e,
title = "Chemical genetic-mediated spatial regulation of protein expression in neurons reveals an axonal function for wld S ",
abstract = "The degeneration of axons is the underlying pathological process of several neurological disorders. The Wallerian degeneration (Wld S) slow protein, which is primarily nuclear, markedly inhibits axonal degeneration. Contradictory models have been proposed to explain its mechanism, including a role in the nucleus, where it affects gene transcription, and roles outside the nucleus, where it regulates unknown effectors. To determine which pool of Wld S accounts for its axon-protective effects, we developed a strategy to control the spatial expression of proteins within neurons. This strategy couples a chemical genetic method to control protein stability with microfluidic culturing. Using neurons that are selectively deficient in Wld S in axons, we show that the axonal pool of Wld S is necessary for protection from axon degeneration. These results implicate an axonal pathway regulated by Wld S that controls axon degeneration.",
author = "Cohen, {Michael S.} and Ghosh, {Ananda K.} and Kim, {Hyung Joon} and Jeon, {Noo Li} and Jaffrey, {Samie R.}",
note = "Funding Information: We thank T. Wandless (Stanford University) for providing DD constructs and advice on their use prior to their publication; F. Lotti and L. Pellizzoni (Columbia University) for providing the lentiviral transfer vector and helper plasmids; M. Toth (Weill Cornell Medical College) for the FMRP construct; M. Coleman (Babraham Institute, UK) for the Wld S construct; J. Harris (University of California, Irvine) for preparing the master for casting microfluidic devices and Jeremy Paige, Alessia Deglincerti, and other members of the Jaffrey laboratory for helpful discussions. This work was supported by a World Class University program through the Korea Research Foundation funded by the Ministry of Education, Science and Technology (R31-2008-000-10083-0) and the Pioneer Research Center Program (2010-0002229) through the National Research Foundation funded by the Ministry of Education (to N.L.J.), Science and Technology; a Life Sciences Research Foundation fellowship (Amgen fellow) and National Institute on Drug Abuse training grant T32DA007274 (to M.S.C.); and a New York State Spinal Cord Injury grant, a Klingenstein Fellowship award in the Neurosciences, the Spinal Muscular Atrophy Foundation, and National Institute of Neurological Disorders and Stroke grant R01 NS056306 (to S.R.J.). N.L.J. is an inventor and patent holder of the microfluidic devices described in this article and is a cofounder of Xona Microfluidics, LLC, which markets related microfluidic devices. ",
year = "2012",
month = feb,
day = "24",
doi = "10.1016/j.chembiol.2012.01.012",
language = "English (US)",
volume = "19",
pages = "179--187",
journal = "Chemistry and Biology",
issn = "1074-5521",
publisher = "Elsevier Inc.",
number = "2",
}