PLEKHA7 Recruits PDZD11 to Adherens Junctions to Stabilize Nectins
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PLEKHA7 Recruits PDZD11 to Adherens Junctions to Stabilize Nectins. / Guerrera, Diego; Shah, Jimit; Vasileva, Ekaterina; Sluysmans, Sophie; Méan, Isabelle; Jond, Lionel; Poser, Ina; Mann, Matthias; Hyman, Anthony A; Citi, Sandra.
In: The Journal of Biological Chemistry, Vol. 291, No. 21, 20.05.2016, p. 11016-29.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - PLEKHA7 Recruits PDZD11 to Adherens Junctions to Stabilize Nectins
AU - Guerrera, Diego
AU - Shah, Jimit
AU - Vasileva, Ekaterina
AU - Sluysmans, Sophie
AU - Méan, Isabelle
AU - Jond, Lionel
AU - Poser, Ina
AU - Mann, Matthias
AU - Hyman, Anthony A
AU - Citi, Sandra
N1 - © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/5/20
Y1 - 2016/5/20
N2 - PLEKHA7 is a junctional protein implicated in stabilization of the cadherin protein complex, hypertension, cardiac contractility, glaucoma, microRNA processing, and susceptibility to bacterial toxins. To gain insight into the molecular basis for the functions of PLEKHA7, we looked for new PLEKHA7 interactors. Here, we report the identification of PDZ domain-containing protein 11 (PDZD11) as a new interactor of PLEKHA7 by yeast two-hybrid screening and by mass spectrometry analysis of PLEKHA7 immunoprecipitates. We show that PDZD11 (17 kDa) is expressed in epithelial and endothelial cells, where it forms a complex with PLEKHA7, as determined by co-immunoprecipitation analysis. The N-terminal Trp-Trp (WW) domain of PLEKHA7 interacts directly with the N-terminal 44 amino acids of PDZD11, as shown by GST-pulldown assays. Immunofluorescence analysis shows that PDZD11 is localized at adherens junctions in a PLEKHA7-dependent manner, because its junctional localization is abolished by knock-out of PLEKHA7, and is rescued by re-expression of exogenous PLEKHA7. The junctional recruitment of nectin-1 and nectin-3 and their protein levels are decreased via proteasome-mediated degradation in epithelial cells where either PDZD11 or PLEKHA7 have been knocked-out. PDZD11 forms a complex with nectin-1 and nectin-3, and its PDZ domain interacts directly with the PDZ-binding motif of nectin-1. PDZD11 is required for the efficient assembly of apical junctions of epithelial cells at early time points in the calcium-switch model. These results show that the PLEKHA7-PDZD11 complex stabilizes nectins to promote efficient early junction assembly and uncover a new molecular mechanism through which PLEKHA7 recruits PDZ-binding membrane proteins to epithelial adherens junctions.
AB - PLEKHA7 is a junctional protein implicated in stabilization of the cadherin protein complex, hypertension, cardiac contractility, glaucoma, microRNA processing, and susceptibility to bacterial toxins. To gain insight into the molecular basis for the functions of PLEKHA7, we looked for new PLEKHA7 interactors. Here, we report the identification of PDZ domain-containing protein 11 (PDZD11) as a new interactor of PLEKHA7 by yeast two-hybrid screening and by mass spectrometry analysis of PLEKHA7 immunoprecipitates. We show that PDZD11 (17 kDa) is expressed in epithelial and endothelial cells, where it forms a complex with PLEKHA7, as determined by co-immunoprecipitation analysis. The N-terminal Trp-Trp (WW) domain of PLEKHA7 interacts directly with the N-terminal 44 amino acids of PDZD11, as shown by GST-pulldown assays. Immunofluorescence analysis shows that PDZD11 is localized at adherens junctions in a PLEKHA7-dependent manner, because its junctional localization is abolished by knock-out of PLEKHA7, and is rescued by re-expression of exogenous PLEKHA7. The junctional recruitment of nectin-1 and nectin-3 and their protein levels are decreased via proteasome-mediated degradation in epithelial cells where either PDZD11 or PLEKHA7 have been knocked-out. PDZD11 forms a complex with nectin-1 and nectin-3, and its PDZ domain interacts directly with the PDZ-binding motif of nectin-1. PDZD11 is required for the efficient assembly of apical junctions of epithelial cells at early time points in the calcium-switch model. These results show that the PLEKHA7-PDZD11 complex stabilizes nectins to promote efficient early junction assembly and uncover a new molecular mechanism through which PLEKHA7 recruits PDZ-binding membrane proteins to epithelial adherens junctions.
KW - Adherens Junctions
KW - Animals
KW - Carrier Proteins
KW - Cell Adhesion Molecules
KW - Dogs
KW - Humans
KW - Madin Darby Canine Kidney Cells
KW - Multiprotein Complexes
KW - Nectins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1074/jbc.M115.712935
DO - 10.1074/jbc.M115.712935
M3 - Journal article
C2 - 27044745
VL - 291
SP - 11016
EP - 11029
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 21
ER -
ID: 186877030