The LIM protein Ajuba is recruited to cadherin-dependent cell junctions through an association with alpha-catenin.
Cell-cell adhesive events affect cell growth and fate decisions and provide spatial clues for cell polarity within tissues. The complete molecular determinants required for adhesive junction formation and their function are not completely understood. LIM domain-containing proteins have been shown to be present at cell-cell contact sites and are known to shuttle into the nucleus where they can affect cell fate and growth; however, their precise localization at cell-cell contacts, how they localize to these sites, and what their functions are at these sites is unknown. Here we show that, in primary keratinocytes, the LIM domain protein Ajuba is recruited to cadherin-dependent cell-cell adhesive complexes in a regulated manner. At cadherin adhesive complexes Ajuba interacts with alpha-catenin, and alpha-catenin is required for efficient recruitment of Ajuba to cell junctions. Ajuba also interacts directly with F-actin. Keratinocytes from Ajuba null mice exhibit abnormal cell-cell junction formation and/or stability and function. These data reveal Ajuba as a new component at cadherin-mediated cell-cell junctions and suggest that Ajuba may contribute to the bridging of the cadherin adhesive complexes to the actin cytoskeleton and as such contribute to the formation or strengthening of cadherin-mediated cell-cell adhesion.
Marie
Helene
H
Medical Research Council Laboratory for Molecular Cell Biology and Department of Physiology, University College London, Gower Street, United Kingdom.
Pratt
Stephen J
SJ
Betson
Martha
M
Epple
Holly
H
Kittler
Josef T
JT
Meek
Laura
L
Moss
Stephen J
SJ
Troyanovsky
Sergey
S
Attwell
David
D
Longmore
Gregory D
GD
Braga
Vania M M
VM
D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion; D002450:Cell Communication; D003598:Cytoskeletal Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology; D060588:LIM Domain Proteins; D051178:alpha Catenin
C485608:AJUBA protein, human; D000199:Actins; C119385:Ajuba protein, rat; C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D051178:alpha Catenin