Toggle Main Menu Toggle Search

Open Access padlockePrints

Ligand-induced internalization of TNF receptor 2 mediated by a di-leucin motif is dispensable for activation of the NFκB pathway

Lookup NU author(s): Dr Anja Krippner-Heidenreich

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Endocytosis is an important mechanism to regulate tumor necrosis factor (TNF) signaling. In contrast to TNF receptor 1 (TNFR1; CD120a), the relevance of receptor internalization for signaling as well as the fate and route of internalized TNF receptor 2 (TNFR2; CD120b) is poorly understood. To analyze the dynamics of TNFR2 signaling and turnover at the plasma membrane we established a human TNFR2 expressing mouse embryonic fibroblast cell line in a TNFR1-/-/TNFR2-/- background. TNF stimulation resulted in a decrease of constitutive TNFR2 ectodomain shedding. We hypothesized that reduced ectodomain release is a result of TNF/TNFR2 complex internalization. Indeed, we could demonstrate that TNFR2 was internalized together with its ligand and cytoplasmic binding partners. Upon endocytosis the TNFR2 signaling complex colocalized with late endosome/lysosome marker Rab7 and entered the lysosomal degradation pathway. Furthermore, we identified a di-leucin motif in the cytoplasmic part of TNFR2 suggesting clathrin-dependent internalization of TNFR2. Internalization defective TNFR2 mutants are capable to signal, i.e. activate NFκB, demonstrating that the di-leucin motif dependent internalization is dispensable for this response. We therefore propose that receptor internalization primarily serves as a negative feed-back to limit TNF responses via TNFR2. © 2010 Elsevier Inc.


Publication metadata

Author(s): Fischer R, Maier O, Naumer M, Krippner-Heidenreich A, Scheurich P, Pfizenmaier K

Publication type: Article

Publication status: Published

Journal: Cellular Signalling

Year: 2011

Volume: 23

Issue: 1

Pages: 161-170

Print publication date: 31/08/2010

ISSN (print): 0898-6568

ISSN (electronic): 1873-3913

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.cellsig.2010.08.016

DOI: 10.1016/j.cellsig.2010.08.016


Altmetrics

Altmetrics provided by Altmetric


Share