Cortactin is necessary for E-cadherin-mediated contact formation and actin reorganization.
Classical cadherin adhesion molecules are key determinants of cell-cell recognition during development and in post-embryonic life. A decisive step in productive cadherin-based recognition is the conversion of nascent adhesions into stable zones of contact. It is increasingly clear that such contact zone extension entails active cooperation between cadherin adhesion and the force-generating capacity of the actin cytoskeleton. Cortactin has recently emerged as an important regulator of actin dynamics in several forms of cell motility. We now report that cortactin is recruited to cell-cell adhesive contacts in response to homophilic cadherin ligation. Notably, cortactin accumulates preferentially, with Arp2/3, at cell margins where adhesive contacts are being extended. Recruitment of cortactin is accompanied by a ligation-dependent biochemical interaction between cortactin and the cadherin adhesive complex. Inhibition of cortactin activity in cells blocked Arp2/3-dependent actin assembly at cadherin adhesive contacts, significantly reduced cadherin adhesive contact zone extension, and perturbed both cell morphology and junctional accumulation of cadherins in polarized epithelia. Together, our findings identify a necessary role for cortactin in the cadherin-actin cooperation that supports productive contact formation.
Helwani
Falak M
FM
Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
Kovacs
Eva M
EM
Paterson
Andrew D
AD
Verma
Suzie
S
Ali
Radiya G
RG
Fanning
Alan S
AS
Weed
Scott A
SA
Yap
Alpha S
AS
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size; D002645:Chickens; D051356:Cortactin; D006224:Cricetinae; D004285:Dogs; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference
D000199:Actins; C495868:CTTN protein, human; D015820:Cadherins; D051356:Cortactin; D046911:Macromolecular Substances; D008840:Microfilament Proteins