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Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility

Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop...

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Detalles Bibliográficos
Autores principales: Ciraolo, Elisa, Morello, Fulvio, Hobbs, Robin M., Wolf, Frieder, Marone, Romina, Iezzi, Manuela, Lu, Xiaoyun, Mengozzi, Giulio, Altruda, Fiorella, Sorba, Giovanni, Guan, Kaomei, Pandolfi, Pier Paolo, Wymann, Matthias P., Hirsch, Emilio
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828958/
https://www.ncbi.nlm.nih.gov/pubmed/20053680
http://dx.doi.org/10.1091/mbc.E09-08-0744
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author Ciraolo, Elisa
Morello, Fulvio
Hobbs, Robin M.
Wolf, Frieder
Marone, Romina
Iezzi, Manuela
Lu, Xiaoyun
Mengozzi, Giulio
Altruda, Fiorella
Sorba, Giovanni
Guan, Kaomei
Pandolfi, Pier Paolo
Wymann, Matthias P.
Hirsch, Emilio
author_facet Ciraolo, Elisa
Morello, Fulvio
Hobbs, Robin M.
Wolf, Frieder
Marone, Romina
Iezzi, Manuela
Lu, Xiaoyun
Mengozzi, Giulio
Altruda, Fiorella
Sorba, Giovanni
Guan, Kaomei
Pandolfi, Pier Paolo
Wymann, Matthias P.
Hirsch, Emilio
author_sort Ciraolo, Elisa
collection PubMed
description Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.
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spelling pubmed-28289582010-05-16 Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility Ciraolo, Elisa Morello, Fulvio Hobbs, Robin M. Wolf, Frieder Marone, Romina Iezzi, Manuela Lu, Xiaoyun Mengozzi, Giulio Altruda, Fiorella Sorba, Giovanni Guan, Kaomei Pandolfi, Pier Paolo Wymann, Matthias P. Hirsch, Emilio Mol Biol Cell Articles Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers. The American Society for Cell Biology 2010-03-01 /pmc/articles/PMC2828958/ /pubmed/20053680 http://dx.doi.org/10.1091/mbc.E09-08-0744 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Ciraolo, Elisa
Morello, Fulvio
Hobbs, Robin M.
Wolf, Frieder
Marone, Romina
Iezzi, Manuela
Lu, Xiaoyun
Mengozzi, Giulio
Altruda, Fiorella
Sorba, Giovanni
Guan, Kaomei
Pandolfi, Pier Paolo
Wymann, Matthias P.
Hirsch, Emilio
Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility
title Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility
title_full Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility
title_fullStr Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility
title_full_unstemmed Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility
title_short Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility
title_sort essential role of the p110β subunit of phosphoinositide 3-oh kinase in male fertility
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828958/
https://www.ncbi.nlm.nih.gov/pubmed/20053680
http://dx.doi.org/10.1091/mbc.E09-08-0744
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