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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...

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Autores principales: Ray, Shayoni, Fanti, Joseph A., Macedo, Diego P., Larsen, Melinda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
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.
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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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