TY - JOUR
T1 - Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex
AU - Choi, Jongho
AU - Troyanovsky, Regina B.
AU - Indra, Indrajyoti
AU - Mitchell, Brian J.
AU - Troyanovsky, Sergey M.
N1 - Funding Information:
We would like to thank Drs. Alex Yemelyanov, Cara Gottardi, Heike Folsch, and Jennifer W. Mitchell (all from Northwestern University, Chicago, IL) for the generous gifts of reagents and comments about the manuscript. Sequencing, flow cytometry, and confocal microscopy were performed at the Northwestern University Genetic, Flow Cytometry, and Advanced Microscopy Centers. The work was supported by grants from the National Institutes of Health: AR44016 and AR057992 (to S.M. Troyanovsky) and GM0113922 (to B.J. Mitchell).
Publisher Copyright:
© 2019 Choi et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
PY - 2019
Y1 - 2019
N2 - The basolateral protein Scribble (Scrib), a member of the LAP protein family, is essential for epithelial apicobasal polarity (ABP) in Drosophila. However, a conserved function for this protein in mammals is unclear. Here we show that the crucial role for Scrib in ABP has remained obscure due to the compensatory function of two other LAP proteins, Erbin and Lano. A combined Scrib/Erbin/Lano knockout disorganizes the cell-cell junctions and the cytoskeleton. It also results in mislocalization of several apical (Par6, aPKC, and Pals1) and basolateral (Llgl1 and Llgl2) identity proteins. These defects can be rescued by the conserved “LU” region of these LAP proteins. Structure-function analysis of this region determined that the so-called LAPSDb domain is essential for basolateral targeting of these proteins, while the LAPSDa domain is essential for supporting the membrane basolateral identity and binding to Llgl. In contrast to the key role in Drosophila, mislocalization of Llgl proteins does not appear to be critical in the scrib ABP phenotype.
AB - The basolateral protein Scribble (Scrib), a member of the LAP protein family, is essential for epithelial apicobasal polarity (ABP) in Drosophila. However, a conserved function for this protein in mammals is unclear. Here we show that the crucial role for Scrib in ABP has remained obscure due to the compensatory function of two other LAP proteins, Erbin and Lano. A combined Scrib/Erbin/Lano knockout disorganizes the cell-cell junctions and the cytoskeleton. It also results in mislocalization of several apical (Par6, aPKC, and Pals1) and basolateral (Llgl1 and Llgl2) identity proteins. These defects can be rescued by the conserved “LU” region of these LAP proteins. Structure-function analysis of this region determined that the so-called LAPSDb domain is essential for basolateral targeting of these proteins, while the LAPSDa domain is essential for supporting the membrane basolateral identity and binding to Llgl. In contrast to the key role in Drosophila, mislocalization of Llgl proteins does not appear to be critical in the scrib ABP phenotype.
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U2 - 10.1083/jcb.201804201
DO - 10.1083/jcb.201804201
M3 - Article
C2 - 31147384
AN - SCOPUS:85069265549
SN - 0021-9525
VL - 218
SP - 2277
EP - 2293
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
ER -