Neurofilaments bind tubulin and modulate its polymerization.
Neurofilaments assemble from three intermediate-filament proteins, contribute to the radial growth of axons, and are exceptionally stable. Microtubules are dynamic structures that assemble from tubulin dimers to support intracellular transport of molecules and organelles. We show here that neurofilaments, and other intermediate-filament proteins, contain motifs in their N-terminal domains that bind unassembled tubulin. Peptides containing such motifs inhibit the in vitro polymerization of microtubules and can be taken up by cultured cells in which they disrupt microtubules leading to altered cell shapes and an arrest of division. In transgenic mice in which neurofilaments are withheld from the axonal compartment, axonal tubulin accumulation is normal but microtubules assemble in excessive numbers. These observations suggest a model in which axonal neurofilaments modulate local microtubule assembly. This capacity also suggests novel mechanisms through which inherited or acquired disruptions in intermediate filaments might contribute to pathogenesis in multiple conditions.
Bocquet
Arnaud
A
Laboratoire Neurobiologie and Transgenese, Unité Propre de Recherche de l'Enseignement Supérieur EA3143, Inserm, Centre Hospitalier Universitaire, 49033 Angers, France.
Berges
Raphael
R
Frank
Ronald
R
Robert
Patrick
P
Peterson
Alan C
AC
Eyer
Joël
J
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014404:Tubulin / Q000378:metabolism* / Q000502:physiology; D050257:Tubulin Modulators / Q000378:metabolism*
C576937:NFL-TBS.40-63 peptide; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D014404:Tubulin; D050257:Tubulin Modulators