Phosphatase Subfamily Laforin

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily Laforin

Laforin is a glucan phosphatase and an adaptor protein.

Evolution

Laforin found in vertebrates, ciliates, alveolates and plants as well as a few scattered additional species including the animals Trichinella (nematode), Branchiostoma (lancelet) and Nematostella (anemone). It has a single human member, EPM2A.

Domain

Laforin typically has an N-terminal CBM20 carbohydrate-binding module and a C-terminal phosphatase domain. The carbohydrate-binding module targets laforin to Lafora inclusion bodies [1, 2]. The phosphatase domain directly dephosphorylates glycogen [3, 4]. Multiple plant homologs lack the CBM20 domain. Epilepsy-caused mutations are found on both domains.

Function

Laforin is a glucan phosphatase [3, 4] and a phosphatase of muscle glycogen synthase (GS1) in polyglucosan bodies (PBs). In Lafora disease (LD), the deficiency of either laforin or the E3 ligase malin causes massive accumulation of less-branched glycogen inclusions, known as Lafora bodies, also called polyglucosan bodies (PBs), in several types of cells including neurons. Once GS1-synthesized polyglucosan accumulates into PBs, laforin recruits malin to the PBs where laforin dephosphorylates, and malin degrades the GS1 in concert with GPBB and AGL1, resulting in a breakdown of polyglucosan [5].

Laforin also dephosphorylates Ser 9 of Glycogen synthase kinase 3 [6].

Laforin also serves as an adaptor protein involved in several physiological pathways [7]. For instance, the complex of laforin and malin modules protein phosphatase 1 regulatory subunit PPP1R3D via ubiquitination [8]. See [7] for details.

DSP4/SEX4 is one of several plant Laforins, and is implicated in breakdown of starch in the chloroplast [9, 10, 10, 10, 10, 11, 12, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26]

References

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