Laforin targets malin to glycogen in Lafora progressive myoclonus epilepsy.
Laforin targets malin to glycogen in Lafora progressive myoclonus epilepsy.
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DOI：
10.1242/dmm.049802
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发表时间：
2023-01-01
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
Glycogen is the largest cytosolic macromolecule and is kept in solution through a regular system of short branches allowing hydration. This structure was thought to solely require balanced glycogen synthase and branching enzyme activities. Deposition of overlong branched glycogen in the fatal epilepsy Lafora disease (LD) indicated involvement of the LD gene products laforin and the E3 ubiquitin ligase malin in regulating glycogen structure. Laforin binds glycogen, and LD-causing mutations disrupt this binding, laforin–malin interactions and malin's ligase activity, all indicating a critical role for malin. Neither malin's endogenous function nor location had previously been studied due to lack of suitable antibodies. Here, we generated a mouse in which the native malin gene is tagged with the FLAG sequence. We show that the tagged gene expresses physiologically, malin localizes to glycogen, laforin and malin indeed interact, at glycogen, and malin's presence at glycogen depends on laforin. These results, and mice, open the way to understanding unknown mechanisms of glycogen synthesis critical to LD and potentially other much more common diseases due to incompletely understood defects in glycogen metabolism. Summary: A new FLAG-malin mouse shows that E3 ubiquitin ligase malin associates with glycogen via laforin, uncovering molecular bases of unknown glycogen metabolism critical to Lafora disease and potentially common diseases.
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影响因子：
3.5
作者：
Ganesh, S;Delgado-Escueta, AV;Yamakawa, K
通讯作者：
Yamakawa, K
影响因子：
3.5
作者：
Akman, H. Orhan;Emmanuele, Valentina;Craigen, William J.
通讯作者：
Craigen, William J.
影响因子：
4.6
作者：
Augé E;Duran J;Guinovart JJ;Pelegrí C;Vilaplana J
通讯作者：
Vilaplana J
影响因子：
5.8
作者：
Brewer MK;Machio-Castello M;Viana R;Wayne JL;Kuchtová A;Simmons ZR;Sternbach S;Li S;García-Gimeno MA;Serratosa JM;Sanz P;Vander Kooi CW;Gentry MS
通讯作者：
Gentry MS
影响因子：
7.3
作者：
HUTCHINS, DA;ROGERS, KJ
通讯作者：
ROGERS, KJ