Modulation of repulsive forces between neurofilaments by sidearm phosphorylation

Sanjay Kumar, Jan H. Hoh

Research output: Contribution to journalArticle

Abstract

Recent studies have advanced the notion that the axonal organization of neurofilaments (NFs) is based on mutual steric repulsion between the unstructured "sidearm" domains of adjacent NFs. Here, we present experimental evidence that these repulsive forces are modulated by the degree of sidearm phosphorylation. When NFs are sedimented into a gelatinous pellet, pellet volume falls with increasing ionic strength and enzymatic dephosphorylation; sedimentation of phosphorylated NFs in the presence of divalent cations also dramatically reduces pellet volume. Further, atomic force microscopy imaging of isolated mammalian NFs reveals robust exclusion of colloidal particles from the NF backbone that is reduced at high ionic strength and attenuated when the filaments are enzymatically dephosphorylated. Phosphate-phosphate repulsion on the NF sidearm appears to modulate NF excluded volume in a graded fashion, thereby controlling axonal NF organization through interfilament forces.

Original languageEnglish (US)
Pages (from-to)489-496
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume324
Issue number2
DOIs
Publication statusPublished - Nov 12 2004

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Keywords

  • Amyotrophic lateral sclerosis
  • Atomic force microscopy
  • Calcium
  • Cell mechanics
  • Cytoskeleton
  • Intermediate filaments
  • Phosphorylation
  • Polyelectrolyte
  • Polymer brush
  • Protein gels
  • Unstructured proteins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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