Limits...
Protection of armadillo/β-Catenin by armless, a novel positive regulator of wingless signaling.

Reim G, Hruzova M, Goetze S, Basler K - PLoS Biol. (2014)

Bottom Line: We found by genetic and biochemical analyses that Als functions downstream of the destruction complex, at the level of the SCF/Slimb/βTRCP E3 Ub ligase.In the absence of Als, Arm levels are severely reduced.We suggest that Als antagonizes Ter94's positive effect on E3 ligase function and propose that Als promotes Wg signaling by rescuing Arm from proteolytic degradation, spotlighting an unexpected step where the Wg pathway signal is modulated.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

ABSTRACT
The Wingless (Wg/Wnt) signaling pathway is essential for metazoan development, where it is central to tissue growth and cellular differentiation. Deregulated Wg pathway activation underlies severe developmental abnormalities, as well as carcinogenesis. Armadillo/β-Catenin plays a key role in the Wg transduction cascade; its cytoplasmic and nuclear levels directly determine the output activity of Wg signaling and are thus tightly controlled. In all current models, once Arm is targeted for degradation by the Arm/β-Catenin destruction complex, its fate is viewed as set. We identified a novel Wg/Wnt pathway component, Armless (Als), which is required for Wg target gene expression in a cell-autonomous manner. We found by genetic and biochemical analyses that Als functions downstream of the destruction complex, at the level of the SCF/Slimb/βTRCP E3 Ub ligase. In the absence of Als, Arm levels are severely reduced. We show by biochemical and in vivo studies that Als interacts directly with Ter94, an AAA ATPase known to associate with E3 ligases and to drive protein turnover. We suggest that Als antagonizes Ter94's positive effect on E3 ligase function and propose that Als promotes Wg signaling by rescuing Arm from proteolytic degradation, spotlighting an unexpected step where the Wg pathway signal is modulated.

Show MeSH

Related in: MedlinePlus

als acts in a cell-autonomous manner.Wg target gene expression (Sens) is affected cell-autonomously upon impaired als function as judged from wing disc analysis at the late L3 stage (A–A″). GFP expression indicates cell clones expressing alsRNAi line oligo310UAS (A and A″). Adult wing phenotypes coincide with cell clones that experienced als depletion, as marked by forked wing hairs (B–E). This is reminiscent of adult wing phenotypes obtained when Wg signaling is impaired (Lgs17E expression) (F–I). Red asterisks (B and F) indicate notches at the wing margin; red arrows (C and G) indicate wing margin notches accompanied by loss of mechano- and sensory bristles; red arrows (D and H) and brackets (E and I) indicate broadened veins.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4219662&req=5

pbio-1001988-g003: als acts in a cell-autonomous manner.Wg target gene expression (Sens) is affected cell-autonomously upon impaired als function as judged from wing disc analysis at the late L3 stage (A–A″). GFP expression indicates cell clones expressing alsRNAi line oligo310UAS (A and A″). Adult wing phenotypes coincide with cell clones that experienced als depletion, as marked by forked wing hairs (B–E). This is reminiscent of adult wing phenotypes obtained when Wg signaling is impaired (Lgs17E expression) (F–I). Red asterisks (B and F) indicate notches at the wing margin; red arrows (C and G) indicate wing margin notches accompanied by loss of mechano- and sensory bristles; red arrows (D and H) and brackets (E and I) indicate broadened veins.

Mentions: To investigate whether Als functions in Wg producing or receiving cells, UAS-alsRNAi was expressed in clones of wing imaginal cells marked by GFP co-expression. Expression of the Wg target Sens was lost in early induced clones (Figure 3A–3A″). This effect is cell-autonomous, i.e., it also occurs when mutant cells are close to wild-type cells that produce Wg. Adult wing clones, marked by UAS-forkedRNAi co-expression, had wing notches and thickened veins (Figure 3B–3E), both of which were tightly associated with mutant cells. We observed similar phenotypes when Wg signaling was cell-autonomously impaired (Figure 3F–3I).


Protection of armadillo/β-Catenin by armless, a novel positive regulator of wingless signaling.

Reim G, Hruzova M, Goetze S, Basler K - PLoS Biol. (2014)

als acts in a cell-autonomous manner.Wg target gene expression (Sens) is affected cell-autonomously upon impaired als function as judged from wing disc analysis at the late L3 stage (A–A″). GFP expression indicates cell clones expressing alsRNAi line oligo310UAS (A and A″). Adult wing phenotypes coincide with cell clones that experienced als depletion, as marked by forked wing hairs (B–E). This is reminiscent of adult wing phenotypes obtained when Wg signaling is impaired (Lgs17E expression) (F–I). Red asterisks (B and F) indicate notches at the wing margin; red arrows (C and G) indicate wing margin notches accompanied by loss of mechano- and sensory bristles; red arrows (D and H) and brackets (E and I) indicate broadened veins.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219662&req=5

pbio-1001988-g003: als acts in a cell-autonomous manner.Wg target gene expression (Sens) is affected cell-autonomously upon impaired als function as judged from wing disc analysis at the late L3 stage (A–A″). GFP expression indicates cell clones expressing alsRNAi line oligo310UAS (A and A″). Adult wing phenotypes coincide with cell clones that experienced als depletion, as marked by forked wing hairs (B–E). This is reminiscent of adult wing phenotypes obtained when Wg signaling is impaired (Lgs17E expression) (F–I). Red asterisks (B and F) indicate notches at the wing margin; red arrows (C and G) indicate wing margin notches accompanied by loss of mechano- and sensory bristles; red arrows (D and H) and brackets (E and I) indicate broadened veins.
Mentions: To investigate whether Als functions in Wg producing or receiving cells, UAS-alsRNAi was expressed in clones of wing imaginal cells marked by GFP co-expression. Expression of the Wg target Sens was lost in early induced clones (Figure 3A–3A″). This effect is cell-autonomous, i.e., it also occurs when mutant cells are close to wild-type cells that produce Wg. Adult wing clones, marked by UAS-forkedRNAi co-expression, had wing notches and thickened veins (Figure 3B–3E), both of which were tightly associated with mutant cells. We observed similar phenotypes when Wg signaling was cell-autonomously impaired (Figure 3F–3I).

Bottom Line: We found by genetic and biochemical analyses that Als functions downstream of the destruction complex, at the level of the SCF/Slimb/βTRCP E3 Ub ligase.In the absence of Als, Arm levels are severely reduced.We suggest that Als antagonizes Ter94's positive effect on E3 ligase function and propose that Als promotes Wg signaling by rescuing Arm from proteolytic degradation, spotlighting an unexpected step where the Wg pathway signal is modulated.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

ABSTRACT
The Wingless (Wg/Wnt) signaling pathway is essential for metazoan development, where it is central to tissue growth and cellular differentiation. Deregulated Wg pathway activation underlies severe developmental abnormalities, as well as carcinogenesis. Armadillo/β-Catenin plays a key role in the Wg transduction cascade; its cytoplasmic and nuclear levels directly determine the output activity of Wg signaling and are thus tightly controlled. In all current models, once Arm is targeted for degradation by the Arm/β-Catenin destruction complex, its fate is viewed as set. We identified a novel Wg/Wnt pathway component, Armless (Als), which is required for Wg target gene expression in a cell-autonomous manner. We found by genetic and biochemical analyses that Als functions downstream of the destruction complex, at the level of the SCF/Slimb/βTRCP E3 Ub ligase. In the absence of Als, Arm levels are severely reduced. We show by biochemical and in vivo studies that Als interacts directly with Ter94, an AAA ATPase known to associate with E3 ligases and to drive protein turnover. We suggest that Als antagonizes Ter94's positive effect on E3 ligase function and propose that Als promotes Wg signaling by rescuing Arm from proteolytic degradation, spotlighting an unexpected step where the Wg pathway signal is modulated.

Show MeSH
Related in: MedlinePlus