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

Exp Mol Med. 2011 Mar 31;43(3):153-60. doi: 10.3858/emm.2011.43.3.019.

Abstract

Phosphatidylinositol phosphates (PtdInsPs) 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 PtdInsPs on this process. We found that PtdInsPs, including PI(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 PtdInsPs 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 PtdInsP. These results collectively suggest that Arg(54) plays a pivotal role in NF-L self assembly by binding with PtdInsPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorescent Antibody Technique
  • Mice
  • Mutation / genetics
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism*
  • Phosphatidylinositol Phosphates / metabolism*
  • Phospholipase C gamma / metabolism
  • Protein Multimerization*

Substances

  • Neurofilament Proteins
  • Phosphatidylinositol Phosphates
  • neurofilament protein L
  • Phospholipase C gamma