SPG4 mutations studied

Process for regulating Spastin levels described


A process leading to decreased Spastin levels associated with certain SPG4 mutations has been defined and described in this Turkish study.


The most common cause of autosomal dominant hereditary spastic paraplegia, that is characterized by axonal degeneration in corticospinal tracts and posterior columns, is known to be caused by mutations in the SPG4 gene which encodes spastin, a microtubule severing ATPase belonging to AAA family. Spastin promotes the formation of microtubule networks that are essential for axon growth and branching, which are important for neuronal plasticity.

Mutations observed in the SPG4 gene of hereditary spastic paraplegia patients have been shown to cause reduced spastin levels. In addition to mutations, transcriptional regulation of spastin gene expression may also affect spastin level. ETS (E Twenty Six-specific)-domain transcription factor, Elk1, has been shown to be important for synaptic plasticity and interact with microtubules. In this study, we aimed to identify the critical promoter regions of the SPG4 gene and the effects of Elk on SPG4 gene expression.

We identified 700 bp TATA-less promoter, including a critical CpG island as an optimal promoter, and deletion of the CpG island gradually decreased the SPG4 promoter activity. In addition, we identified the binding sites of Elk1 on the SPG4 promoter by EMSA. Over-expression of Elk1 showed that it repressed the SPG4 promoter and also decreased spastin protein level in SHSY-5Y cells.


SOURCE: J Neurochem. 2011 May;117(4):724-34. doi: 10.1111/j.1471-4159.2011.07243.x.

SPG4 gene promoter regulation via Elk1 transcription factor.

Canbaz D, Kırımtay K, Karaca E, Karabay A.

Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.

© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.


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