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Alternative splicing results in RET isoforms with distinct trafficking properties
RET encodes a receptor tyrosine kinase that is essential for spermatogenesis, development of the sensory, sympathetic, parasympathetic, and enteric nervous systems and the kidneys, as well as for maintenance of adult midbrain dopaminergic neurons. RET is alternatively spliced to encode multiple isof...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459860/ https://www.ncbi.nlm.nih.gov/pubmed/22875993 http://dx.doi.org/10.1091/mbc.E12-02-0114 |
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author | Richardson, Douglas S. Rodrigues, David M. Hyndman, Brandy D. Crupi, Mathieu J. F. Nicolescu, Adrian C. Mulligan, Lois M. |
author_facet | Richardson, Douglas S. Rodrigues, David M. Hyndman, Brandy D. Crupi, Mathieu J. F. Nicolescu, Adrian C. Mulligan, Lois M. |
author_sort | Richardson, Douglas S. |
collection | PubMed |
description | RET encodes a receptor tyrosine kinase that is essential for spermatogenesis, development of the sensory, sympathetic, parasympathetic, and enteric nervous systems and the kidneys, as well as for maintenance of adult midbrain dopaminergic neurons. RET is alternatively spliced to encode multiple isoforms that differ in their C-terminal amino acids. The RET9 and RET51 isoforms display unique levels of autophosphorylation and have differential interactions with adaptor proteins. They induce distinct gene expression patterns, promote different levels of cell differentiation and transformation, and play unique roles in development. Here we present a comprehensive study of the subcellular localization and trafficking of RET isoforms. We show that immature RET9 accumulates intracellularly in the Golgi, whereas RET51 is efficiently matured and present in relatively higher amounts on the plasma membrane. RET51 is internalized faster after ligand binding and undergoes recycling back to the plasma membrane. This differential trafficking of RET isoforms produces a more rapid and longer duration of signaling through the extracellular-signal regulated kinase/mitogen-activated protein kinase pathway downstream of RET51 relative to RET9. Together these differences in trafficking properties contribute to some of the functional differences previously observed between RET9 and RET51 and establish the important role of intracellular trafficking in modulating and maintaining RET signaling. |
format | Online Article Text |
id | pubmed-3459860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34598602012-12-16 Alternative splicing results in RET isoforms with distinct trafficking properties Richardson, Douglas S. Rodrigues, David M. Hyndman, Brandy D. Crupi, Mathieu J. F. Nicolescu, Adrian C. Mulligan, Lois M. Mol Biol Cell Articles RET encodes a receptor tyrosine kinase that is essential for spermatogenesis, development of the sensory, sympathetic, parasympathetic, and enteric nervous systems and the kidneys, as well as for maintenance of adult midbrain dopaminergic neurons. RET is alternatively spliced to encode multiple isoforms that differ in their C-terminal amino acids. The RET9 and RET51 isoforms display unique levels of autophosphorylation and have differential interactions with adaptor proteins. They induce distinct gene expression patterns, promote different levels of cell differentiation and transformation, and play unique roles in development. Here we present a comprehensive study of the subcellular localization and trafficking of RET isoforms. We show that immature RET9 accumulates intracellularly in the Golgi, whereas RET51 is efficiently matured and present in relatively higher amounts on the plasma membrane. RET51 is internalized faster after ligand binding and undergoes recycling back to the plasma membrane. This differential trafficking of RET isoforms produces a more rapid and longer duration of signaling through the extracellular-signal regulated kinase/mitogen-activated protein kinase pathway downstream of RET51 relative to RET9. Together these differences in trafficking properties contribute to some of the functional differences previously observed between RET9 and RET51 and establish the important role of intracellular trafficking in modulating and maintaining RET signaling. The American Society for Cell Biology 2012-10-01 /pmc/articles/PMC3459860/ /pubmed/22875993 http://dx.doi.org/10.1091/mbc.E12-02-0114 Text en © 2012 Richardson 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 BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Richardson, Douglas S. Rodrigues, David M. Hyndman, Brandy D. Crupi, Mathieu J. F. Nicolescu, Adrian C. Mulligan, Lois M. Alternative splicing results in RET isoforms with distinct trafficking properties |
title | Alternative splicing results in RET isoforms with distinct trafficking properties |
title_full | Alternative splicing results in RET isoforms with distinct trafficking properties |
title_fullStr | Alternative splicing results in RET isoforms with distinct trafficking properties |
title_full_unstemmed | Alternative splicing results in RET isoforms with distinct trafficking properties |
title_short | Alternative splicing results in RET isoforms with distinct trafficking properties |
title_sort | alternative splicing results in ret isoforms with distinct trafficking properties |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459860/ https://www.ncbi.nlm.nih.gov/pubmed/22875993 http://dx.doi.org/10.1091/mbc.E12-02-0114 |
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