Figure 3

Disturbed interaction between CRMP-2 and kinesin light chain in MS. Tetrameric CRMP-2, may act as a cargo protein transporting molecules such as α- and β-tubulin heterodimers anterogradely with the aid of kinesin-1. CRMP-2 can be phosphorylated or cleaved during MS and this phosphorylation inhibits its binding to molecules impairing axonal transport. Inhibition of α- and β-tubulin heterodimers can promote the disassembly of polymerized microtubules. During MS, increased free calpain may potentiate cleavage of CRMP-2, impairing its function, leading to the failure of axonal transport and inevitably neurodegeneration. (A) (Top) Immunoprecipitation of CRMP-2, of brain white matter lysates from both non-neurological disease control (NNDC) and MS patients, followed by western immunoblot analysis using the monoclonal anti-kinesin light chain (KLC) antibody. (Bottom) Western immunoblot for KLC from the same brain samples loaded pre-immunoprecipitation (5% input of immunoprecipitation sample) using the monoclonal anti-KLC antibody. (B) Densitometric quantification (AU) of total KLC and KLC (after immunoprecipitation) from white matter lysates of NNDC and MS (n = 3; **P < 0.01, student’s t-test). (C) Concept diagram illustrating either cleavage or phosphorylation of CRMP-2 during MS culminating in the interference of the interaction between CRMP-2 with tubulin heterodimers and kinesin light chain, leading to microtubule disassembly.