Restricted Scope. Diversity Supplement for Kyle Auger: Regulation, signaling, and dynamics of glucan phosphatases

  • Gentry, Matthew (PI)

Grants and Contracts Details


This project focuses on and expands Aim 3 Translate current insights into patient-specific diagnosis and treatment of the funded R01. The Sub-Aim is entitled: Defining specific mechanisms of LD laforin mutations. The laforin structure opens exciting new avenues for defining LD mutations at the atomic level. These data will serve as a platform, allowing us to understand how specific patient mutations result in LD. This structure, coupled with a suite of assays we have developed, will allow us to define a patient’s specific structural mechanism for LD laforin mutations. Kyle will perform master and perform a number of experimental protocols to define LD patient mutations at the atomic level. There are 33 laforin point mutations scattered between laforin’s CBM and DSP domain. The CBM is responsible for glycogen binding, and the DSP possesses phosphatase activity. In addition to these two functions, laforin interacts with other proteins and some mutations disrupt protein-protein interactions. Thus, there are four classes of laforin mutations: 1) destabilized protein, 2) disrupted glycogen binding, 3) decreased/abolished phosphatase activity, and 4) disrupted protein-protein interactions. Since establishing laforin as the first glucan phosphatase we have modified existing assays and developed novel assays to monitor its activity. This suite of assays allows us to probe the ability of laforin to both bind and dephosphorylate glycogen. Our ability to quantitatively define laforin binding to glycogen is one area that needs to be improved. Kyle’s work will focus developing assays in this area.
Effective start/end date7/1/104/30/16


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