Phosphatidylinositol phosphates directly bind to neurofilament light chain (NF-L) for the regulation of NF-L self assembly

Abstract

Phosphatidylinositol phosphates (PtdlnsPs) are ubiquitous membrane phospholipids that play diverse roles in cell growth and differentiation. To clarify the regulation mechanism acting on neurofilament light chain (NF-L) self assembly, we examined the effects of various PtdlnsPs on this process. We found that PtdlnsPs, including Pl(4,5)P(2), directly bind to the positively charged Arg(54) of murine NF-L, and this binding promotes NF-L self assembly in vitro. Mutant NF-L (R53A/R54A) proteins lacking binding affinity to PtdlnsPs did not have the same effect, but the mutant NF-L proteins showed greater self assembly than the wild-type in the absence of any PtdlnsP. These results collectively suggest that Arg54 plays a pivotal role in NF-L self assembly by binding with PtdlnsPs.