A surprising analogy between plant metabolism and a fatal form of epilepsy

press release of April 24, 2006

Researchers at the National Centre of Competence in Research (NCCR) Plant Survival participated in the discovery of unexpected genetic similarities between starch metabolism in plants and a fatal form of epilepsy, Lafora disease. Stemming from an international collaboration, the study has been published in the Journal of Biological Chemistry.   

Samuel C. Zeeman, assistant professor at the Swiss Federal Institute of Technology in Zurich (ETHZ), and his colleagues are studying the genes involved in starch metabolism in plants. Thanks to an international collaboration with the universities of Berne (CH), Durham (UK), Edinburgh (UK) and Western Australia, they succeeded in identifying a genetic mutation in Arabidopsis thaliana that causes an abnormal accumulation of starch.

Starch is the main form of carbohydrates that is stored in plants. It is synthesised throughout the day during photosynthesis and accumulates in the leaves. During the night, the stored starch is degraded into sucrose, a sugar that is directly used by plants. The NCCR Plant Survival team and their colleagues have discovered that mutations of a novel gene preventing the synthesis of the SEX4 (starch-excess 4) protein cause an abnormal accumulation of starch. The scientists believe SEX4 is essential for controlling the transformation of starch into sucrose.

The researchers also noted that the structure of the SEX4 proteins closely resembles that of laforin, which is associated with the Lafora disease. In fact, mutations that affect the function of laforin in humans and mice cause the premature death of neurons, resulting in severe and involuntary muscular spasms, which is a characteristic of epilepsy.

Lafora disease is a rare hereditary pathology that belongs to the group of progressive myoclonus epilepsies. The first symptoms appear at around the age of fifteen with a slow degeneration of the nervous system followed by a deterioration of cerebral functions. The affected person ends up loosing his or her autonomy and can no longer move, speak and feed unaided. Death occurs within twenty years of onset.

The unexpected link with plant biology relates to the origin of the disease: neuronal death in Lafora patients is caused by an abnormal accumulation of glycogen in tissues. Normally, glycogen acts as a reservoir of glucose (sugar) in animals. Specific proteins, such as laforin, control the formation and subsequent breakdown of glycogen. Genetic defects that inhibit the proper synthesis of those proteins are at the origin of the Lafora disease.    

"The similarity between the control of starch and glycogen metabolism is surprising", says Samuel C. Zeeman. "What makes it so surprising is the fact that the metabolisms of glycogen in animals and of starch in plants are significantly different." It is unlikely that research on plants will directly lead to therapeutic solutions for Lafora disease, nevertheless, the existence of analogous genes in the plant kingdom to those that control laforin in humans helps to better understand the mechanisms of the progressive epilepsies.    

Original article:

Similar protein phosphatases control starch metabolism in plants and glycogen metabolism in mammals.

Niittylä T, Comparot-Moss S, Lue WL, Messerli G, Trevisan M, Seymour MD, Gatehouse JA, Villadsen D, Smith SM, Chen J, Zeeman SC, Smith AM. J Biol Chem. 2006 Mar 2

The full text is available at: http://www.jbc.org/cgi/reprint/M600519200v1




Prof. Samuel C. Zeeman
E-mail: szeeman(at)ethz.ch
tel +41 44 632 8275

Gaëlle Messerli
E-mail: mgaelle(at)ethz.ch
tel +41 44 632 3824