Document Detail


Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis.
MedLine Citation:
PMID:  19874813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Juxtamembrane signaling via the membrane growth factor KitL is critical for Kit mediated functions. KitL has a conserved cytoplasmic domain and has been shown to possess a monomeric leucine-dependent basolateral targeting signal. To investigate the consequences in vivo of impaired basolateral KitL targeting in polarized epithelial cells, we have mutated this critical leucine to alanine using a knock-in strategy. KitL(L263A/L263A) mutant mice are pigmented normally and steady-state hematopoiesis is unaffected although peritoneal and skin mast cell numbers are significantly increased. KitL localization is affected in the Sertoli cells of the KitL(L263A/L263A) testis and testis size is reduced in these mice due to aberrant spermatogonial proliferation. Furthermore, the effect of the KitL L263A mutation on the testicular phenotype is dosage dependent. The tubules of hemizygous KitL(L263A/Sl) mice completely lack germ cells in contrast to the weaker testicular phenotype of KitL(L263A/L263A) mice. The onset of the testis phenotype coincides with the formation of tight junctions between Sertoli cells during postnatal development. Thus, the altered sorting of KitL is dispensable for hematopoietic and melanogenic lineages, yet is crucial in the testicular environment, where the basal membranes of adjacent polarized Sertoli cells form a niche for the proliferating spermatogonia.
Authors:
Shayu Deshpande; Valter Agosti; Katia Manova; Malcolm A S Moore; Matthew P Hardy; Peter Besmer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-10-27
Journal Detail:
Title:  Developmental biology     Volume:  337     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-02-25     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-210     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Affiliation:
Developmental Biology, Sloan-Kettering Institute, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis
Cell Count
Cell Polarity*
Cell Proliferation
Exons / genetics
Gene Targeting
Hematopoiesis / physiology*
Lymphopoiesis
Male
Mast Cells / cytology
Mice
Molecular Sequence Data
Mutation / genetics
Protein Structure, Tertiary
Protein Transport
Sequence Deletion
Spermatogenesis / physiology*
Stem Cell Factor / chemistry*,  metabolism*
Structure-Activity Relationship
Testis / metabolism,  pathology
Grant Support
ID/Acronym/Agency:
R01 HD 38908/HD/NICHD NIH HHS; R01 HD038908-19/HD/NICHD NIH HHS; R01 HL/DK55748/DK/NIDDK NIH HHS; R01 HL051031-08/HL/NHLBI NIH HHS; R01 HL055748-05A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Stem Cell Factor
Comments/Corrections

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