Molecular pathogenesis of Charcot-Marie-Tooth Diseases
As the most common genetic neuromuscular disorder, the Charcot-Marie-Tooth Diseases (CMT) are now associated with mutations in more than 80 genes. I have focused on the genes associated with the ‘demyelinating’ subtype of CMT, where Schwann cell dysfunction is deemed to be the underlying pathological mechanism. Interestingly, many of these affected genes encode proteins with known or predicted roles in intracellular membrane trafficking. There are no current treatments for CMT, and my goal is to characterize the molecular and cell biological roles of factors that are mutated in CMT, with the hope of developing informed future therapies.
Sh3tc2 localizes to Schwann cells that surround teased rat sciatic nerve fibres. The myelin sheath is shown in red (labeled for myelin basic protein) and sh3tc2 is shown in green located in the cytoplasm of the surrounding Schwann cell (blue nuclei).
Vijay S, Chiu M, Dacks JB, Roberts RC. Exclusive expression of the Rab11 effector SH3TC2 in Schwann cells links integrin-α6 and myelin maintenance to Charcot-Marie-Tooth disease type 4C. Biochim Biophys Acta 1862(7):1279-1290 doi: 10.1016/j.bbadis.2016.04.003 (2016).
Roberts RC et al. Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C. Hum. Mol. Genet. 19, 1009–1018 (2010).
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