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RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding

Joris Wauman (UGent) , Leentje De Ceuninck (UGent) , Nele Vanderroost (UGent) , Sam Lievens (UGent) and Jan Tavernier (UGent)
(2011) JOURNAL OF CELL SCIENCE. 124(6). p.921-932
Author
Organization
Abstract
Cytokines, such as interferons, erythropoietin, leptin and most interleukins, signal through type 1 cytokine receptors and activate the canonical JAK-STAT pathway. Aberrant cytokine signalling underlies numerous pathologies and adequate, temporary receptor activation is therefore under tight control. Negative-feedback mechanisms are very well studied, but cellular sensitivity also depends on the number of receptors exposed at the cell surface. This is determined by the equilibrium between receptor synthesis and transport to the plasma membrane, internalisation and recycling, degradation and ectodomain shedding, but the molecular basis of how cells establish steady state receptor levels is poorly understood. Here, we report that ring finger protein 41 (RNF41, also known as E3 ubiquitin-protein ligase Nrdp1) interacts with JAK2-associated cytokine receptor complexes and modulates their cell surface exposure and signalling. Moreover, ectopic expression of RNF41 affected turnover of leptin, leukaemia inhibitory factor and interleukin-6 receptor in a dual way: it blocked intracellular cathepsin-L-dependent receptor cleavage and concomitantly enhanced receptor shedding by metalloproteases of the ADAM family. Receptor degradation and shedding are thus interconnected phenomena with a single protein, RNF41, determining the balance.
Keywords
MAPPIT, Ectodomain shedding, RNF41, Nrdp1, Type 1 cytokine receptor, ADAM, CELL-SURFACE EXPRESSION, UBIQUITIN LIGASE NRDP1, LEPTIN RECEPTOR, ERYTHROPOIETIN RECEPTOR, PROTEINS, PATHWAY, ENDOCYTOSIS, ACTIVATION, STABILITY, ENZYME, Cathepsin L cleavage

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Chicago
Wauman, Joris, Leentje De Ceuninck, Nele Vanderroost, Sam Lievens, and Jan Tavernier. 2011. “RNF41 (Nrdp1) Controls Type 1 Cytokine Receptor Degradation and Ectodomain Shedding.” Journal of Cell Science 124 (6): 921–932.
APA
Wauman, J., De Ceuninck, L., Vanderroost, N., Lievens, S., & Tavernier, J. (2011). RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding. JOURNAL OF CELL SCIENCE, 124(6), 921–932.
Vancouver
1.
Wauman J, De Ceuninck L, Vanderroost N, Lievens S, Tavernier J. RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding. JOURNAL OF CELL SCIENCE. 2011;124(6):921–32.
MLA
Wauman, Joris, Leentje De Ceuninck, Nele Vanderroost, et al. “RNF41 (Nrdp1) Controls Type 1 Cytokine Receptor Degradation and Ectodomain Shedding.” JOURNAL OF CELL SCIENCE 124.6 (2011): 921–932. Print.
@article{1208413,
  abstract     = {Cytokines, such as interferons, erythropoietin, leptin and most interleukins, signal through type 1 cytokine receptors and activate the canonical JAK-STAT pathway. Aberrant cytokine signalling underlies numerous pathologies and adequate, temporary receptor activation is therefore under tight control. Negative-feedback mechanisms are very well studied, but cellular sensitivity also depends on the number of receptors exposed at the cell surface. This is determined by the equilibrium between receptor synthesis and transport to the plasma membrane, internalisation and recycling, degradation and ectodomain shedding, but the molecular basis of how cells establish steady state receptor levels is poorly understood. Here, we report that ring finger protein 41 (RNF41, also known as E3 ubiquitin-protein ligase Nrdp1) interacts with JAK2-associated cytokine receptor complexes and modulates their cell surface exposure and signalling. Moreover, ectopic expression of RNF41 affected turnover of leptin, leukaemia inhibitory factor and interleukin-6 receptor in a dual way: it blocked intracellular cathepsin-L-dependent receptor cleavage and concomitantly enhanced receptor shedding by metalloproteases of the ADAM family. Receptor degradation and shedding are thus interconnected phenomena with a single protein, RNF41, determining the balance.},
  author       = {Wauman, Joris and De Ceuninck, Leentje and Vanderroost, Nele and Lievens, Sam and Tavernier, Jan},
  issn         = {0021-9533},
  journal      = {JOURNAL OF CELL SCIENCE},
  keyword      = {MAPPIT,Ectodomain shedding,RNF41,Nrdp1,Type 1 cytokine receptor,ADAM,CELL-SURFACE EXPRESSION,UBIQUITIN LIGASE NRDP1,LEPTIN RECEPTOR,ERYTHROPOIETIN RECEPTOR,PROTEINS,PATHWAY,ENDOCYTOSIS,ACTIVATION,STABILITY,ENZYME,Cathepsin L cleavage},
  language     = {eng},
  number       = {6},
  pages        = {921--932},
  title        = {RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding},
  url          = {http://dx.doi.org/10.1242/jcs.078055},
  volume       = {124},
  year         = {2011},
}

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