A role for myosin-1A in the localization of a brush border disaccharidase

J Cell Biol. 2004 May 10;165(3):395-405. doi: 10.1083/jcb.200310031.

Abstract

To gain insight regarding myosin-1A (M1A) function, we expressed a dominant negative fragment of this motor in the intestinal epithelial cell line, CACO-2BBE. Sucrase isomaltase (SI), a transmembrane disaccharidase found in microvillar lipid rafts, was missing from the brush border (BB) in cells expressing this fragment. Density gradient centrifugation, affinity purification, and immunopurification of detergent-resistant membranes isolated from CACO-2BBE cells and rat microvilli (MV) all indicate that M1A and SI reside on the same population of low density (approximately 1.12 g/ml) membranes. Chemical cross-linking of detergent-resistant membranes from rat MV indicates that SI and M1A may interact in a lipid raft complex. The functional significance of such a complex is highlighted by expression of the cytoplasmic domain of SI, which results in lower levels of M1A and a loss of SI from the BB. Together, these studies are the first to assign a specific role to M1A and suggest that this motor is involved in the retention of SI within the BB.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism*
  • Cell Membrane / enzymology*
  • Cell Membrane / ultrastructure
  • Digestion / physiology
  • Disaccharides / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Intestinal Mucosa / enzymology*
  • Intestinal Mucosa / ultrastructure
  • Membrane Microdomains / metabolism
  • Membrane Microdomains / ultrastructure
  • Microvilli / enzymology
  • Microvilli / ultrastructure
  • Myosin Heavy Chains
  • Myosin Type I
  • Protein Structure, Tertiary / physiology
  • Rats
  • Subcellular Fractions
  • Sucrase-Isomaltase Complex / metabolism*

Substances

  • Calmodulin-Binding Proteins
  • Disaccharides
  • MYO1A protein, human
  • Sucrase-Isomaltase Complex
  • Myosin Type I
  • Myosin Heavy Chains