The myotubularin (MTMR) family of phosphoinositide (PI) 3-phosphatases specifically catalyze the dephosphorylation of phosphatidylinositol 3-phosphate (PI3P) and 3,5-disphosphate (PI(3,5)P2), two lipids that regulate membrane traffic within the endosomal-lysosomal pathway. A number of studies have shown that phosphoinositide regulation in endosomal-lysosomal pathways is critical for functional myelination. This is highlighted by seven disease-causing mutations in human endosomal-related genes (FIG4, MTMR2, MTMR5, MTMR13, FRABIN/FGD4, SH3TC2 and SIMPLE/LITAF) that cause demyelinating forms of Charcot-Marie-Tooth (CMT) peripheral neuropathy. The research performed in this dissertation further characterizes our CMT4B mouse model and describes the localization of endogenous mouse Mtmr2 and Mtmr13 proteins in Schwann cells.
