Myosin II isoforms identify distinct functional modules that support integrity of the epithelial zonula adherens.
Classic cadherin receptors cooperate with regulators of the actin cytoskeleton to control tissue organization in health and disease. At the apical junctions of epithelial cells, the cadherin ring of the zonula adherens (ZA) couples with a contiguous ring of actin filaments to support morphogenetic processes such as tissue integration and cellular morphology. However, the molecular mechanisms that coordinate adhesion and cytoskeleton at these junctions are poorly understood. Previously we identified non-muscle myosin II as a target of Rho signalling that supports cadherin junctions in mammalian epithelial cells. Myosin II has various cellular functions, which are increasingly attributable to the specific biophysical properties and regulation of its different isoforms. Here we report that myosin II isoforms have distinct and necessary roles at cadherin junctions. Although two of the three mammalian myosin II isoforms are found at the ZA, their localization is regulated by different upstream signalling pathways. Junctional localization of myosin IIA required E-cadherin adhesion, Rho/ROCK and myosin light-chain kinase, whereas junctional myosin IIB depended on Rap1. Further, these myosin II isoforms support E-cadherin junction integrity by different mechanisms. Myosin IIA RNA-mediated interference (RNAi) selectively perturbed the accumulation of E-cadherin in the apical ZA, decreased cadherin homophilic adhesion and disrupted cadherin clustering. In contrast, myosin IIB RNAi decreased filament content, altered dynamics, and increased the lateral movement of the perijunctional actin ring. Myosin IIA and IIB therefore identify two distinct functional modules, with different upstream signals that control junctional localization, and distinct functional effects. We propose that these two isoform-based modules cooperate to coordinate adhesion receptor and F-actin organization to form apical cadherin junctions.
Smutny
Michael
M
Institute for Molecular Bioscience, Division of Molecular Cell Biology, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
Cox
Hayley L
HL
Leerberg
Joanne M
JM
Kovacs
Eva M
EM
Conti
Mary Anne
MA
Ferguson
Charles
C
Hamilton
Nicholas A
NA
Parton
Robert G
RG
Adelstein
Robert S
RS
Yap
Alpha S
AS
D022005:Adherens Junctions / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008954:Models, Biological; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*
D015820:Cadherins; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB