Refined Analysis of Protein Interaction between L-periaxin and DRP2

Periaxin is a cytoskeletal-associated protein that was initially identified in peripheral nervous system, and periaxin has been confirmed to play an essential role in myelination and myelin maintenance. DRP2 is the only reported protein to interact with periaxin, but the accurate binding mechanism of DRP2 and L-periaxin is still not clear. In this report, the interaction between L-periaxin and DRP2 was further investigated by bimolecular fluorescence complementation (BiFC), Co-IP, GST pull-down, fluorescence spectroscopy, and subcellular localization. The result demonstrated that L-periaxin possesses three unusual nuclear localization signals, NLS1 of the NLS domain involved in nucleocytoplasmic shuttling of L-periaxin protein, both NLS2 and NLS3 of the NLS domain participated in interaction with spectrin-like domain 2 and WW domain of DRP2. These data revealed a previously unknown binding model between DRP2 and L-periaxin, and provided valuable data for finding the relationship between L-periaxin and pathogenesis of demyelinating Charcot Marie tooth type 4F disease.