TY - JOUR
T1 - The NF2 Tumor Suppressor, Merlin, Regulates Epidermal Development through the Establishment of a Junctional Polarity Complex
AU - Gladden, Andrew B.
AU - Hebert, Alan M.
AU - Schneeberger, Eveline E.
AU - McClatchey, Andrea I.
N1 - Funding Information:
We thank members of the McClatchey laboratory for helpful discussions and B. Morgan for comments on the manuscript. Par3 expression plasmids were graciously provided by I. Macara (University of Virginia). We thank M. Giovannini (House Ear Institute) for the Nf2 lox/lox mice, T. Pawson (Mount Sinai Hospital, Toronto) for the aPKC expression plasmid, W. Weis (Stanford University) for GST AJ constructs and R. Fehon (University of Chicago) for Ez and Ez Δactin expression plasmids. The work was supported by an NRSA fellowship (5F32CA124030) awarded to A.B.G. and by grants from the NIH (R01 CA113733), DOD (W81XWH-05-1-0189) and O'Brien Trust awarded to A.I.M.
PY - 2010/11/16
Y1 - 2010/11/16
N2 - The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a FERM (Four point one, Ezrin, Radixin, Moesin) domain-containing protein whose loss results in defective morphogenesis and tumorigenesis in multiple tissues. Like the closely related ERM proteins (Ezrin, Radixin, and Moesin), Merlin may organize the plasma membrane by assembling membrane protein complexes and linking them to the cortical actin cytoskeleton. We previously found that Merlin is a critical mediator of contact-dependent inhibition of proliferation and is required for the establishment of stable adherens junctions (AJs) in cultured cells. Here, we delineate the molecular function of Merlin in AJ establishment in epidermal keratinocytes in vitro and confirm that a role in AJ establishment is an essential function of Merlin in vivo. Our studies reveal that Merlin can associate directly with α-catenin and link it to Par3, thereby providing an essential link between the AJ and the Par3 polarity complex during junctional maturation.
AB - The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a FERM (Four point one, Ezrin, Radixin, Moesin) domain-containing protein whose loss results in defective morphogenesis and tumorigenesis in multiple tissues. Like the closely related ERM proteins (Ezrin, Radixin, and Moesin), Merlin may organize the plasma membrane by assembling membrane protein complexes and linking them to the cortical actin cytoskeleton. We previously found that Merlin is a critical mediator of contact-dependent inhibition of proliferation and is required for the establishment of stable adherens junctions (AJs) in cultured cells. Here, we delineate the molecular function of Merlin in AJ establishment in epidermal keratinocytes in vitro and confirm that a role in AJ establishment is an essential function of Merlin in vivo. Our studies reveal that Merlin can associate directly with α-catenin and link it to Par3, thereby providing an essential link between the AJ and the Par3 polarity complex during junctional maturation.
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U2 - 10.1016/j.devcel.2010.10.008
DO - 10.1016/j.devcel.2010.10.008
M3 - Article
C2 - 21074722
AN - SCOPUS:78149476036
SN - 1534-5807
VL - 19
SP - 727
EP - 739
JO - Developmental cell
JF - Developmental cell
IS - 5
ER -