Document Detail


GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells.
MedLine Citation:
PMID:  18363967     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Well-organized spermatogenesis, including the maintenance of spermatogonial stem cells (SSCs), is indispensable for continuous male fertility. Signaling by glial cell line-derived neurotrophic factor (GDNF) via the RET/GDNF family receptor alpha1 (GFRalpha1) receptor complex is essential for self-renewal of murine SSCs and may also regulate their differentiation. When phosphorylated, tyrosine 1062 in RET presents a binding site for the phosphotyrosine-binding domains of several adaptor and effector proteins that are important for activation of a variety of intracellular signaling pathways. In this study, we investigated the role of signaling via RET tyrosine 1062 in spermatogenesis using RET Y1062F knockin mice (Y1062F mice), in which tyrosine 1062 was replaced with phenylalanine. Homozygous Y1062F mice showed marked atrophy of testes due to reduced production of germ cells. RET-expressing spermatogonia in seminiferous tubules of homozygous Y1062F mice decreased after postnatal day (P) 7 and germ cells were almost undetectable by P21. These phenomena appeared to be due to a lack of SSC self-renewal and inability to maintain the undifferentiated state. Our findings suggest that RET signaling via tyrosine 1062 is essential for self-renewal of SSCs and regulation of their differentiation.
Authors:
Mayumi Jijiwa; Kumi Kawai; Jun Fukihara; Akari Nakamura; Masaki Hasegawa; Chikage Suzuki; Tomoko Sato; Atsushi Enomoto; Naoya Asai; Yoshiki Murakumo; Masahide Takahashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes to cells : devoted to molecular & cellular mechanisms     Volume:  13     ISSN:  1365-2443     ISO Abbreviation:  Genes Cells     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-26     Completed Date:  2008-04-16     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9607379     Medline TA:  Genes Cells     Country:  England    
Other Details:
Languages:  eng     Pagination:  365-74     Citation Subset:  IM    
Affiliation:
Department of Pathology, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / cytology*,  metabolism
Amino Acid Substitution
Animals
Apoptosis
Glial Cell Line-Derived Neurotrophic Factor / physiology*
Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
Male
Mice
Mice, Transgenic
Phenotype
Phosphorylation
Proto-Oncogene Proteins c-ret / chemistry*,  genetics,  physiology*
Recombinant Proteins / chemistry,  genetics,  metabolism
Signal Transduction
Spermatogenesis / physiology
Spermatogonia / cytology*,  metabolism
Testis / cytology
Tyrosine / chemistry
Chemical
Reg. No./Substance:
0/Gdnf protein, mouse; 0/Gfra1 protein, mouse; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Glial Cell Line-Derived Neurotrophic Factor Receptors; 0/Recombinant Proteins; 55520-40-6/Tyrosine; EC 2.7.10.1/Proto-Oncogene Proteins c-ret; EC 2.7.10.1/Ret protein, mouse

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