DataSets / Project home (Myotubularins in abscission)
Myotubularin-related proteins 3 & 4 interact with PLK1 and CEP55 to control CEP55 recruitment to the midbody
First Author: Nicole St-Denis
  The myotubularins are a family of phosphatases that dephosphorylate the phosphatidylinositols PI3P and PI3,5P. Several family members are mutated in disease, yet the biological functions of the majority of myotubularins remain unknown. To gain insight into the roles of the individual enzymes, we have used affinity purification coupled to mass spectrometry (AP-MS) to identify protein-protein interactions for the myotubularins. The resultant interactome includes 66 high confidence (FDR ≤1%) interactions, including 18 pairwise interactions between individual myotubularins. The results reveal a variety of new signalling contexts for the family of enzymes, including an intriguing, novel role for MTMR3 and MTMR4 in the regulation of abscission, the final step of mitosis in which the membrane bridge remaining between two daughter cells is cleaved. Both depletion and overexpression of either MTMR3 or MTMR4 results in abnormal midbody morphology and cytokinetic failure. Interestingly, MTMR3 and MTMR4 do not exert their effects through lipid regulation at the midbody, but regulate abscission during early mitosis, by forming interactions with CEP55, an important regulator of abscission, and PLK1, a master mitotic kinase. These interactions are crucial for the proper recruitment of CEP55, and subsequently ESCRT-I, to the midbody. This work provides the first biological function reported for MTMR3/4 heterodimers, and demonstrates the temporal and spatial complexity of mitotic signaling.

See our publication at Mol Cell Proteomics.

The raw mass spectrometry data was contributed to ProteomeXchange through the MassIVE repository.