Phosphoinositides (PIs) are a group of low abundance phospholipids that play a critical role in the control of organelle and membrane traffic. There is strong evidence that specific PIs are also important for the regulation of autophagy. PIs are modified by a complex network of lipid kinases and phosphatases. A recent study from our laboratory focused on two PI phosphatases from the myotubularin related protein (MTMR) family, myotubularin (MTM1) and MTMR14. Using zebrafish as a model system, we found that dual knockdown of MTM1 and MTMR14 leads to an unexpectedly severe developmental motor phenotype. We found that this severe phenotype was mediated, at least in part, by dysregulation of autophagy, as demonstrated by the accumulation of autophagic vacuoles and increased levels of LC3-II. Our study provides the first in vivo evidence for a role of myotubularins, and in particular MTMR14, in the regulation of autophagy.
JJ Dowling, SE Low, AS Busta, EL Feldman. Zebrafish MTMR14 is required for excitation-contraction coupling, developmental motor function and the regulation of autophagy. Hum Mol Genet 2010; 19: 2668- 81.
PMID: 20400459 DOI: 10.1093/hmg/ddq153