Copyright © 2006 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 79, Issue 2, 351-357, 1 August 2006
doi:10.1086/504927
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ZFYVE27 (SPG33), a Novel Spastin-Binding Protein, Is Mutated in Hereditary Spastic Paraplegia
Ashraf U. Mannana, 
, 
, Philip Krawena, Simone M. Sautera, Johann Boehma, Agnieszka Chronowskaa, Walter Paulusb, Juergen Neesena, * and Wolfgang Engela
a From the Institute of Human Genetics, University of Goettingen, Goettingen, Germany
b Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany
Address for correspondence and reprints: Dr. Ashraf U. Mannan, Institute of Human Genetics, University of Goettingen, Heinrich-Dueker Weg 12, D-37073, Goettingen, Germany* Present affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Department of Human Genetics, Medical University of Vienna, Vienna.
Abstract
Spastin, the most commonly mutated protein in the autosomal dominant form of hereditary spastic paraplegia (AD-HSP) has been suggested to be involved in vesicular cargo trafficking; however, a comprehensive function of spastin has not yet been elucidated. To characterize the molecular function of spastin, we used the yeast two-hybrid approach to identify new interacting partners of spastin. Here, we report ZFYVE27, a novel member of the FYVE-finger family of proteins, as a specific spastin-binding protein, and we validate the interaction by both in vivo coimmunoprecipitation and colocalization experiments in mammalian cells. More importantly, we report a German family with AD-HSP in which ZFYVE27 (SPG33) is mutated; furthermore, we demonstrate that the mutated ZFYVE27 protein shows an aberrant intracellular pattern in its tubular structure and that its interaction with spastin is severely affected. We postulate that this specific mutation in ZFYVE27 affects neuronal intracellular trafficking in the corticospinal tract, which is consistent with the pathology of HSP.
Article Information
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