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LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis
Coordinated actin microfilament and microtubule dynamics is required for salivary gland development, although the mechanisms by which they contribute to branching morphogenesis are not defined. Because LIM kinase (LIMK) regulates both actin and microtubule organization, we investigated the role of L...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142612/ https://www.ncbi.nlm.nih.gov/pubmed/24966172 http://dx.doi.org/10.1091/mbc.E14-02-0705 |
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author | Ray, Shayoni Fanti, Joseph A. Macedo, Diego P. Larsen, Melinda |
author_facet | Ray, Shayoni Fanti, Joseph A. Macedo, Diego P. Larsen, Melinda |
author_sort | Ray, Shayoni |
collection | PubMed |
description | Coordinated actin microfilament and microtubule dynamics is required for salivary gland development, although the mechanisms by which they contribute to branching morphogenesis are not defined. Because LIM kinase (LIMK) regulates both actin and microtubule organization, we investigated the role of LIMK signaling in mouse embryonic submandibular salivary glands using ex vivo organ cultures. Both LIMK 1 and 2 were necessary for branching morphogenesis and functioned to promote epithelial early- and late-stage cleft progression through regulation of both microfilaments and microtubules. LIMK-dependent regulation of these cytoskeletal systems was required to control focal adhesion protein–dependent fibronectin assembly and integrin β1 activation, involving the LIMK effectors cofilin and TPPP/p25, for assembly of the actin- and tubulin-based cytoskeletal systems, respectively. We demonstrate that LIMK regulates the early stages of cleft formation—cleft initiation, stabilization, and progression—via establishment of actin stability. Further, we reveal a novel role for the microtubule assembly factor p25 in regulating stabilization and elongation of late-stage progressing clefts. This study demonstrates the existence of multiple actin- and microtubule-dependent stabilization steps that are controlled by LIMK and are required in cleft progression during branching morphogenesis. |
format | Online Article Text |
id | pubmed-4142612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-41426122014-10-30 LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis Ray, Shayoni Fanti, Joseph A. Macedo, Diego P. Larsen, Melinda Mol Biol Cell Articles Coordinated actin microfilament and microtubule dynamics is required for salivary gland development, although the mechanisms by which they contribute to branching morphogenesis are not defined. Because LIM kinase (LIMK) regulates both actin and microtubule organization, we investigated the role of LIMK signaling in mouse embryonic submandibular salivary glands using ex vivo organ cultures. Both LIMK 1 and 2 were necessary for branching morphogenesis and functioned to promote epithelial early- and late-stage cleft progression through regulation of both microfilaments and microtubules. LIMK-dependent regulation of these cytoskeletal systems was required to control focal adhesion protein–dependent fibronectin assembly and integrin β1 activation, involving the LIMK effectors cofilin and TPPP/p25, for assembly of the actin- and tubulin-based cytoskeletal systems, respectively. We demonstrate that LIMK regulates the early stages of cleft formation—cleft initiation, stabilization, and progression—via establishment of actin stability. Further, we reveal a novel role for the microtubule assembly factor p25 in regulating stabilization and elongation of late-stage progressing clefts. This study demonstrates the existence of multiple actin- and microtubule-dependent stabilization steps that are controlled by LIMK and are required in cleft progression during branching morphogenesis. The American Society for Cell Biology 2014-08-15 /pmc/articles/PMC4142612/ /pubmed/24966172 http://dx.doi.org/10.1091/mbc.E14-02-0705 Text en © 2014 Ray et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Ray, Shayoni Fanti, Joseph A. Macedo, Diego P. Larsen, Melinda LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
title | LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
title_full | LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
title_fullStr | LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
title_full_unstemmed | LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
title_short | LIM kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
title_sort | lim kinase regulation of cytoskeletal dynamics is required for salivary gland branching morphogenesis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142612/ https://www.ncbi.nlm.nih.gov/pubmed/24966172 http://dx.doi.org/10.1091/mbc.E14-02-0705 |
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