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Statements

Subject Item
n2:RIV%2F00216208%3A11310%2F13%3A10189085%21RIV14-MSM-11310___
rdf:type
skos:Concept n10:Vysledek
rdfs:seeAlso
http://dx.doi.org/10.1371/journal.pone.0076971
dcterms:description
In C. elegans and Drosophila, retromer mediated retrograde transport of Wntless (Wls) from endosomes to the trans-Golgi network (TGN) is required for Wnt secretion. When this retrograde transport pathway is blocked, Wls is missorted to lysosomes and degraded, resulting in reduced Wnt secretion and various Wnt related phenotypes. In the mammalian intestine, Wnt signaling is essential to maintain stem cells. This prompted us to ask if retromer mediated Wls recycling is also important for Wnt signaling and stem cell maintenance in this system. To answer this question, we generated a conditional Vps35(fl) allele. As Vps35 is an essential subunit of the retromer complex, this genetic tool allowed us to inducibly interfere with retromer function in the intestinal epithelium. Using a pan-intestinal epithelial Cre line (Villin-CreERT2), we did not observe defects in crypt or villus morphology after deletion of Vps35 from the intestinal epithelium. Wnt secreted from the mesenchyme of the intestine may compensate for a reduction in epithelial Wnt secretion. To exclude the effect of the mesenchyme, we generated intestinal organoid cultures. Loss of Vps35 in intestinal organoids did not affect the overall morphology of the organoids. We were able to culture Vps35(Delta/Delta) organoids for many passages without Wnt supplementation in the growth medium. However, Wls protein levels were reduced and we observed a subtle growth defect in the Vps35(Delta/Delta) organoids. These results confirm the role of retromer in the retrograde trafficking of Wls in the intestine, but show that retromer mediated Wls recycling is not essential to maintain Wnt signaling or stem cell proliferation in the intestinal epithelium. In C. elegans and Drosophila, retromer mediated retrograde transport of Wntless (Wls) from endosomes to the trans-Golgi network (TGN) is required for Wnt secretion. When this retrograde transport pathway is blocked, Wls is missorted to lysosomes and degraded, resulting in reduced Wnt secretion and various Wnt related phenotypes. In the mammalian intestine, Wnt signaling is essential to maintain stem cells. This prompted us to ask if retromer mediated Wls recycling is also important for Wnt signaling and stem cell maintenance in this system. To answer this question, we generated a conditional Vps35(fl) allele. As Vps35 is an essential subunit of the retromer complex, this genetic tool allowed us to inducibly interfere with retromer function in the intestinal epithelium. Using a pan-intestinal epithelial Cre line (Villin-CreERT2), we did not observe defects in crypt or villus morphology after deletion of Vps35 from the intestinal epithelium. Wnt secreted from the mesenchyme of the intestine may compensate for a reduction in epithelial Wnt secretion. To exclude the effect of the mesenchyme, we generated intestinal organoid cultures. Loss of Vps35 in intestinal organoids did not affect the overall morphology of the organoids. We were able to culture Vps35(Delta/Delta) organoids for many passages without Wnt supplementation in the growth medium. However, Wls protein levels were reduced and we observed a subtle growth defect in the Vps35(Delta/Delta) organoids. These results confirm the role of retromer in the retrograde trafficking of Wls in the intestine, but show that retromer mediated Wls recycling is not essential to maintain Wnt signaling or stem cell proliferation in the intestinal epithelium.
dcterms:title
Retromer Dependent Recycling of the Wnt Secretion Factor Wls Is Dispensable for Stem Cell Maintenance in the Mammalian Intestinal Epithelium Retromer Dependent Recycling of the Wnt Secretion Factor Wls Is Dispensable for Stem Cell Maintenance in the Mammalian Intestinal Epithelium
skos:prefLabel
Retromer Dependent Recycling of the Wnt Secretion Factor Wls Is Dispensable for Stem Cell Maintenance in the Mammalian Intestinal Epithelium Retromer Dependent Recycling of the Wnt Secretion Factor Wls Is Dispensable for Stem Cell Maintenance in the Mammalian Intestinal Epithelium
skos:notation
RIV/00216208:11310/13:10189085!RIV14-MSM-11310___
n10:predkladatel
n11:orjk%3A11310
n4:aktivita
n12:I
n4:aktivity
I
n4:cisloPeriodika
10
n4:dodaniDat
n14:2014
n4:domaciTvurceVysledku
n9:2910055
n4:druhVysledku
n13:J
n4:duvernostUdaju
n18:S
n4:entitaPredkladatele
n20:predkladatel
n4:idSjednocenehoVysledku
102741
n4:idVysledku
RIV/00216208:11310/13:10189085
n4:jazykVysledku
n8:eng
n4:klicovaSlova
stem cell; vps35; wntless; retromer; trans-golgi network
n4:klicoveSlovo
n6:wntless n6:stem%20cell n6:retromer n6:vps35 n6:trans-golgi%20network
n4:kodStatuVydavatele
ES - Španělské království
n4:kontrolniKodProRIV
[072719E3FA3E]
n4:nazevZdroje
PLoS ONE
n4:obor
n17:EB
n4:pocetDomacichTvurcuVysledku
1
n4:pocetTvurcuVysledku
6
n4:rokUplatneniVysledku
n14:2013
n4:svazekPeriodika
8
n4:tvurceVysledku
Clevers, Hans C. de Groot, Reinoud E. A. Farin, Henner F. van Es, Johan H. Korswagen, Hendrik C. Macůrková, Marie
n4:wos
000325810900113
s:issn
1932-6203
s:numberOfPages
9
n19:doi
10.1371/journal.pone.0076971
n15:organizacniJednotka
11310