The cadherin-11 cytoplasmic juxtamembrane domain promotes alpha-catenin turnover at adherens junctions and intercellular motility.
Cadherins mediate homophilic cell adhesion and contribute to tissue morphogenesis and architecture. Cadherin cell adhesion contacts are actively remodeled and impact cell movement and migration over other cells. We found that expression of a mutant cadherin-11 lacking the cytoplasmic juxtamembrane domain (JMD) diminished the turnover of alpha-catenin at adherens junctions as measured by fluorescence recovery after photobleaching. This resulted in markedly diminished cell intercalation into monolayers reflecting reduced cadherin-11-dependent cell motility on other cells. Furthermore, the actin cytoskeleton in cadherin-11 deltaJMD cells revealed a more extensive cortical F-actin ring that correlated with significantly higher levels of activated Rac1. Together, these data implicate the cadherin-11 cytoplasmic JMD as a regulator of alpha-catenin turnover at adherens junctions and actin-cytoskeletal organization that is critical for intercellular motility and rearrangement in multicellular clusters.
Kiener
Hans P
HP
Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Stipp
Christopher S
CS
Allen
Philip G
PG
Higgins
Jonathan M G
JM
Brenner
Michael B
MB
D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D009154:Mutation; D051178:alpha Catenin / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D051178:alpha Catenin; C086960:osteoblast cadherin; D020830:rac1 GTP-Binding Protein