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Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes
Melanosomes are melanin-containing organelles that provide pigmentation and protection from solar UV radiation to the skin. In melanocytes, melanosomes mature and traffic to dendritic tips, where they are transferred to adjacent epidermal keratinocytes through pathways that involve microtubule netwo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185957/ https://www.ncbi.nlm.nih.gov/pubmed/32049584 http://dx.doi.org/10.1091/mbc.E19-09-0510 |
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author | Crawford, Melissa Liu, Nancy Mahdipour, Elahe Barr, Kevin Heit, Bryan Dagnino, Lina |
author_facet | Crawford, Melissa Liu, Nancy Mahdipour, Elahe Barr, Kevin Heit, Bryan Dagnino, Lina |
author_sort | Crawford, Melissa |
collection | PubMed |
description | Melanosomes are melanin-containing organelles that provide pigmentation and protection from solar UV radiation to the skin. In melanocytes, melanosomes mature and traffic to dendritic tips, where they are transferred to adjacent epidermal keratinocytes through pathways that involve microtubule networks and the actin cytoskeleton. However, the role of scaffold proteins in these processes is poorly understood. Integrin-linked kinase (ILK) is a scaffold protein that regulates microtubule stability and F-actin dynamics. Here we show that ILK is necessary for normal trafficking of melanosomes along microtubule tracks. In the absence of ILK, immature melanosomes are not retained in perinuclear regions, and mature melanosome trafficking along microtubule tracks is impaired. These deficits can be attenuated by microtubule stabilization. Microtubules are also necessary for the formation of dendrites in melanocytes, and Ilk inactivation reduces melanocyte dendricity. Activation of glycogen synthase kinase-3 (GSK-3) interferes with microtubule assembly. Significantly, inhibition of GSK-3 activity or exogenous expression of the GSK-3 substrate collapsin response mediator protein 2 (CRMP2) in ILK-deficient melanocytes restored dendricity. ILK is also required for normal melanin transfer, and GSK-3 inhibition in melanocytes partially restored melanin transfer to neighboring keratinocytes. Thus, our work shows that ILK is a central modulator of melanosome movements in primary epidermal melanocytes and identifies ILK and GSK-3 as important modulators of melanin transfer to keratinocytes, a key process for epidermal UV photoprotection. |
format | Online Article Text |
id | pubmed-7185957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-71859572020-06-16 Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes Crawford, Melissa Liu, Nancy Mahdipour, Elahe Barr, Kevin Heit, Bryan Dagnino, Lina Mol Biol Cell Articles Melanosomes are melanin-containing organelles that provide pigmentation and protection from solar UV radiation to the skin. In melanocytes, melanosomes mature and traffic to dendritic tips, where they are transferred to adjacent epidermal keratinocytes through pathways that involve microtubule networks and the actin cytoskeleton. However, the role of scaffold proteins in these processes is poorly understood. Integrin-linked kinase (ILK) is a scaffold protein that regulates microtubule stability and F-actin dynamics. Here we show that ILK is necessary for normal trafficking of melanosomes along microtubule tracks. In the absence of ILK, immature melanosomes are not retained in perinuclear regions, and mature melanosome trafficking along microtubule tracks is impaired. These deficits can be attenuated by microtubule stabilization. Microtubules are also necessary for the formation of dendrites in melanocytes, and Ilk inactivation reduces melanocyte dendricity. Activation of glycogen synthase kinase-3 (GSK-3) interferes with microtubule assembly. Significantly, inhibition of GSK-3 activity or exogenous expression of the GSK-3 substrate collapsin response mediator protein 2 (CRMP2) in ILK-deficient melanocytes restored dendricity. ILK is also required for normal melanin transfer, and GSK-3 inhibition in melanocytes partially restored melanin transfer to neighboring keratinocytes. Thus, our work shows that ILK is a central modulator of melanosome movements in primary epidermal melanocytes and identifies ILK and GSK-3 as important modulators of melanin transfer to keratinocytes, a key process for epidermal UV photoprotection. The American Society for Cell Biology 2020-04-01 /pmc/articles/PMC7185957/ /pubmed/32049584 http://dx.doi.org/10.1091/mbc.E19-09-0510 Text en © 2020 Crawford et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Crawford, Melissa Liu, Nancy Mahdipour, Elahe Barr, Kevin Heit, Bryan Dagnino, Lina Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
title | Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
title_full | Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
title_fullStr | Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
title_full_unstemmed | Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
title_short | Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
title_sort | integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185957/ https://www.ncbi.nlm.nih.gov/pubmed/32049584 http://dx.doi.org/10.1091/mbc.E19-09-0510 |
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