E-cadherin/hmr-1 membrane enrichment is polarized by wave-dependent branched actin

Luigy Cordova-Burgos; Falshruti B. Patel; Martha C. Soto

doi:https://doi.org/10.3390/jdb9020019

E-cadherin/hmr-1 membrane enrichment is polarized by wave-dependent branched actin

Luigy Cordova-Burgos, Falshruti B. Patel, Martha C. Soto

Robert Wood Johnson Medical School (RWJMS), Pathology

Rutgers, The State University

Research output: Contribution to journal › Article › peer-review

Abstract

Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical–basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.

Original language	English (US)
Article number	19
Journal	Journal of Developmental Biology
Volume	9
Issue number	2
DOIs	https://doi.org/10.3390/jdb9020019
State	Published - 2021

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

Keywords

Apical junctions
Branched actin
Cadherin
Epithelial polarity

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https://doi.org/10.3390/jdb9020019

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title = "E-cadherin/hmr-1 membrane enrichment is polarized by wave-dependent branched actin",

abstract = "Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical–basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.",

keywords = "Apical junctions, Branched actin, Cadherin, Epithelial polarity",

author = "Luigy Cordova-Burgos and Patel, {Falshruti B.} and Soto, {Martha C.}",

note = "Funding Information: Funding: This research was funded by a grant from the National Institutes of Health (NIH) (GM081670) to M.C.S. and used a Spinning Disk Microscope acquired through an NIH Shared Instrumentation Grant (1S10OD010572) to M.C.S. Funding Information: Acknowledgments: We thank the NCRR-funded Caenorhabditis Genetics Center (CGC), funded by NIH Office of Research Infrastructure Programs (P40 OD010440), for strains. We thank members of the Soto Lab for comments, Daniel Shaye for clone pDS355 used to make the OX966 strain, Figure 2, Elmira Kirichenko for helping build the OX974 strain used in Figure 2E, and Raj Patel for help with EM. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

doi = "https://doi.org/10.3390/jdb9020019",

language = "English (US)",

volume = "9",

journal = "Journal of Developmental Biology",

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T1 - E-cadherin/hmr-1 membrane enrichment is polarized by wave-dependent branched actin

AU - Cordova-Burgos, Luigy

AU - Patel, Falshruti B.

AU - Soto, Martha C.

N1 - Funding Information: Funding: This research was funded by a grant from the National Institutes of Health (NIH) (GM081670) to M.C.S. and used a Spinning Disk Microscope acquired through an NIH Shared Instrumentation Grant (1S10OD010572) to M.C.S. Funding Information: Acknowledgments: We thank the NCRR-funded Caenorhabditis Genetics Center (CGC), funded by NIH Office of Research Infrastructure Programs (P40 OD010440), for strains. We thank members of the Soto Lab for comments, Daniel Shaye for clone pDS355 used to make the OX966 strain, Figure 2, Elmira Kirichenko for helping build the OX974 strain used in Figure 2E, and Raj Patel for help with EM. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical–basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.

AB - Polarized epithelial cells adhere to each other at apical junctions that connect to the apical F-actin belt. Regulated remodeling of apical junctions supports morphogenesis, while dysregulated remodeling promotes diseases such as cancer. We have documented that branched actin regulator, WAVE, and apical junction protein, Cadherin, assemble together in developing C. elegans embryonic junctions. If WAVE is missing in embryonic epithelia, too much Cadherin assembles at apical membranes, and yet apical F-actin is reduced, suggesting the excess Cadherin is not fully functional. We proposed that WAVE supports apical junctions by regulating the dynamic accumulation of Cadherin at membranes. To test this model, here we examine if WAVE is required for Cadherin membrane enrichment and apical–basal polarity in a maturing epithelium, the post-embryonic C. elegans intestine. We find that larval and adult intestines have distinct apicobasal populations of Cadherin, each with distinct dependence on WAVE branched actin. In vivo imaging shows that loss of WAVE components alters post-embryonic E-cadherin membrane enrichment, especially at apicolateral regions, and alters the lateral membrane. Analysis of a biosensor for PI(4,5)P2 suggests loss of WAVE or Cadherin alters the polarity of the epithelial membrane. EM (electron microscopy) illustrates lateral membrane changes including separations. These findings have implications for understanding how mutations in WAVE and Cadherin may alter cell polarity.

KW - Apical junctions

KW - Branched actin

KW - Cadherin

KW - Epithelial polarity

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JF - Journal of Developmental Biology

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E-cadherin/hmr-1 membrane enrichment is polarized by wave-dependent branched actin

Abstract

ASJC Scopus subject areas

Keywords

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