Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis Journal Article

   

Authors:	Deshpande, S.; Agosti, V.; Manova, K.; Moore, M. A. S.; Hardy, M. P.; Besmer, P.
Article Title:	Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis
Abstract:	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. KitLL263A/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 KitLL263A/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 KitLL263A/Sl mice completely lack germ cells in contrast to the weaker testicular phenotype of KitLL263A/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. © 2009 Elsevier Inc. All rights reserved.
Keywords:	immunohistochemistry; controlled study; gene mutation; mutation; exons; sequence deletion; nonhuman; flow cytometry; protein domain; protein function; protein localization; cell proliferation; protein blood level; animal cell; mouse; phenotype; animals; mice; animal tissue; gene targeting; mus; stem cell factor; apoptosis; steady state; germ cell; in vivo study; immunofluorescence; structure-activity relationship; b lymphocyte; tight junction; amino acid sequence; molecular sequence data; western blotting; protein transport; epithelium cell; cytoplasm; cell polarity; cell count; hematopoiesis; protein structure, tertiary; testosterone blood level; proliferation; leucine; site directed mutagenesis; lymphopoiesis; testosterone; thymocyte; testis; polarization; mutant; skin cell; postnatal development; spermatogenesis; lymphoid differentiation; mast cell; sertoli cell; spermatogonia; peritoneum mast cell; testis size; mast cells
Journal Title:	Developmental Biology
Volume:	337
Issue:	2
ISSN:	0012-1606
Publisher:	Elsevier Inc.
Date Published:	2010-01-15
Start Page:	199
End Page:	210
Language:	English
DOI:	10.1016/j.ydbio.2009.10.022
PUBMED:	19874813
PROVIDER:	scopus
PMCID:	PMC2812647
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-72649090019&partnerID=40&md5=7361c66442f74fd603cba736359033ce
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: DEBIA" - "Source: Scopus"

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