Possible role of direct Rac1-Rab7 interaction in ruffled border formation of osteoclasts

J Biol Chem. 2005 Sep 16;280(37):32356-61. doi: 10.1074/jbc.M414213200. Epub 2005 Jul 21.

Abstract

Rab7 has been shown to regulate the late steps of the endocytic pathway. In bone-resorbing osteoclasts, it is involved in formation of the ruffled border, which is a late endosomal-like compartment in the plasma membrane. Here we report a new Rab7-interacting protein, Rac1, another small GTPase protein that binds to the GTP-form of Rab7 as found with a two-hybrid system. We demonstrate further that Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts. In other cell types, such as fibroblast-like cells, partial colocalization is perinuclear. Because Rac1 is known to control the actin cytoskeleton through its effectors, the Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments enabling endosomal vesicles to switch tracks and may thus also regulate ruffled border formation in osteoclasts.

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport
  • Bone Marrow Cells / cytology
  • Bone Resorption
  • Cell Membrane / metabolism
  • Cytoskeleton / metabolism
  • DNA, Complementary / metabolism
  • Endocytosis
  • Endosomes / metabolism
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique, Indirect
  • GTP Phosphohydrolases / chemistry
  • Gene Library
  • Glutathione Transferase / metabolism
  • Histidine / chemistry
  • Intracellular Membranes / metabolism
  • Microscopy, Confocal
  • Models, Biological
  • Molecular Sequence Data
  • Osteoclasts / metabolism*
  • Plasmids / metabolism
  • Protein Binding
  • Rats
  • Two-Hybrid System Techniques
  • rab GTP-Binding Proteins / chemistry*
  • rab7 GTP-Binding Proteins
  • rac1 GTP-Binding Protein / chemistry*

Substances

  • Actins
  • DNA, Complementary
  • rab7 GTP-Binding Proteins
  • rab7 GTP-binding proteins, rat
  • Histidine
  • Glutathione Transferase
  • GTP Phosphohydrolases
  • rab GTP-Binding Proteins
  • rac1 GTP-Binding Protein

Associated data

  • GENBANK/AY491395