Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease

Mittal, Shuchi ; Upadhyay, Mamta ; Kumar Singh, Pankaj ; Parihar, Rashmi ; Ganesh, Subramaniam (2015) Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease Journal of Biosciences, 40 (5). pp. 863-871. ISSN 0250-5991

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Official URL: http://www.ias.ac.in/describe/article/jbsc/040/05/...

Related URL: http://dx.doi.org/10.1007/s12038-015-9570-0

Abstract

Lafora disease (LD), an autosomal recessive and fatal form of neurodegenerative disorder, is characterized by the presence of polyglucosan inclusions in the affected tissues including the brain. LD can be caused by defects either in the EPM2A gene coding for the laforin protein phosphatase or the NHLRC1 gene coding for the malin ubiquitin ligase. Since the clinical symptoms of LD patients representing the two genetic groups are very similar and since malin is known to interact with laforin, we were curious to examine the possibility that the two proteins regulate each other's function. Using cell biological assays we demonstrate here that (i) malin promotes its own degradation via autoubiquitination, (ii) laforin prevents the auto-degradation of malin by presenting itself as a substrate and (iii) malin preferentially degrades the phosphatase-inactive laforin monomer. Our results that laforin and malin regulate each other's stability and activity offers a novel and attractive model to explain the molecular basis of locus heterogeneity observed in LD.

Item Type:Article
Source:Copyright of this article belongs to Indian Academy of Sciences.
Keywords:Epilepsy; Locus Heterogeneity; Post-Translational Modification; Protein-Protein Interaction
ID Code:101674
Deposited On:03 Feb 2017 16:51
Last Modified:03 Feb 2017 16:51

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