Article abstract
Nature Neuroscience 10, 177 - 185 (2007)
Published online: 14 January 2007 | doi:10.1038/nn1841
Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules
Xinnan Wang1, W Robert Shaw1,3, Hilda T H Tsang2, Evan Reid2 & Cahir J O'Kane1
Abstract
To understand the functions of NIPA1, mutated in the neurodegenerative disease hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive congenital ichthyosis, we have studied their Drosophila melanogaster ortholog, spichthyin (Spict). Spict is found on early endosomes. Loss of Spict leads to upregulation of bone morphogenetic protein (BMP) signaling and expansion of the neuromuscular junction. BMP signaling is also necessary for a normal microtubule cytoskeleton and axonal transport; analysis of loss- and gain-of-function phenotypes indicate that Spict may antagonize this function of BMP signaling. Spict interacts with BMP receptors and promotes their internalization from the plasma membrane, implying that it inhibits BMP signaling by regulating BMP receptor traffic. This is the first demonstration of a role for a hereditary spastic paraplegia protein or ichthyin family member in a specific signaling pathway, and implies disease mechanisms for hereditary spastic paraplegia that involve dependence of the microtubule cytoskeleton on BMP signaling.
- Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.
- Department of Medical Genetics, and Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK.
- Present address: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Correspondence to: Cahir J O'Kane1 e-mail: c.okane@gen.cam.ac.uk
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