title: Spermatogenesis rescue in a mouse deficient for the ubiquitin ligase SCF{beta}-TrCP by single substrate depletion.
abstract: beta-TrCP, the substrate recognition subunit of a Skp1-Cul1-F-box (SCF) ubiquitin ligase, is ubiquitously expressed from two distinct paralogs, targeting many regulatory proteins for proteasomal degradation. We generated inducible beta-TrCP hypomorphic mice and found that they are surprisingly healthy, yet have a severe testicular defect. We show that the two beta-TrCP paralogs have a nonredundant role in spermatogenesis. The testicular defect is tightly associated with cell adhesion failure within the seminiferous tubules and is fully reversible upon beta-TrCP restoration. Remarkably, testicular depletion of a single beta-TrCP substrate, Snail1, rescued the adhesion defect and restored spermatogenesis. Our studies highlight an unexpected functional reserve of this central E3, as well as a bottleneck in a specific tissue: a single substrate whose stabilization is incompatible with testicular differentiation.
authors.affiliation: The Lautenberg Center for Immunology, Jerusalem, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Kanarek
authors.forename: Elad
authors.initials: E
authors.lastname: Horwitz
authors.forename: Inbal
authors.initials: I
authors.lastname: Mayan
authors.forename: Michael
authors.initials: M
authors.lastname: Leshets
authors.forename: Gady
authors.initials: G
authors.lastname: Cojocaru
authors.forename: Matti
authors.initials: M
authors.lastname: Davis
authors.forename: Ben-Zion
authors.initials: BZ
authors.lastname: Tsuberi
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarsky
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Yinon
authors.initials: Y
authors.lastname: Ben-Neriah
mesh_terms: D000818:Animals; D007365:Intercellular Junctions / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010641:Phenotype; D020033:Protein Isoforms; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000196:embryology* / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D044843:SKP Cullin F-Box Protein Ligases