A new role for the architecture of microvillar actin bundles in apical retention of membrane proteins

Mol Biol Cell. 2012 Jan;23(2):324-36. doi: 10.1091/mbc.E11-09-0765. Epub 2011 Nov 23.

Abstract

Actin-bundling proteins are identified as key players in the morphogenesis of thin membrane protrusions. Until now, functional redundancy among the actin-bundling proteins villin, espin, and plastin-1 has prevented definitive conclusions regarding their role in intestinal microvilli. We report that triple knockout mice lacking these microvillar actin-bundling proteins suffer from growth delay but surprisingly still develop microvilli. However, the microvillar actin filaments are sparse and lack the characteristic organization of bundles. This correlates with a highly inefficient apical retention of enzymes and transporters that accumulate in subapical endocytic compartments. Myosin-1a, a motor involved in the anchorage of membrane proteins in microvilli, is also mislocalized. These findings illustrate, in vivo, a precise role for local actin filament architecture in the stabilization of apical cargoes into microvilli. Hence, the function of actin-bundling proteins is not to enable microvillar protrusion, as has been assumed, but to confer the appropriate actin organization for the apical retention of proteins essential for normal intestinal physiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Actins / ultrastructure
  • Animals
  • Enterocytes / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / ultrastructure
  • Mice
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Microfilament Proteins / ultrastructure
  • Microscopy, Electron, Transmission
  • Microvilli / metabolism
  • Microvilli / ultrastructure
  • Myosin Heavy Chains / metabolism
  • Protein Structure, Tertiary

Substances

  • Actins
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Myo1a protein, mouse
  • espin protein, mouse
  • plastin
  • villin
  • Myosin Heavy Chains