Impact of TNF-R1 and CD95 Internalization on Apoptotic and Antiapoptotic Signaling
Overview
Affiliations
Internalization of cell surface receptors has long been regarded as a pure means to terminate signaling via receptor degradation. A growing body of information points to the fact that many internalized receptors are still in their active state and that signaling continues along the endocytic pathway. Thus endocytosis orchestrates cell signaling by coupling and integrating different cascades on the surface of endocytic vesicles to control the quality, duration, intensity, and distribution of signaling events. The death receptors tumor necrosis factor-receptor 1 (TNF-R1) and CD95 (Fas, APO-1) are known not only to signal for cell death via apoptosis but are also capable of inducing antiapoptotic signals via transcription factor NF-kappaB induction or activation of the proliferative mitogen-activated protein kinase (MAPK)/ERK (extracellular signal-regulated kinase) protein kinase cascades, resulting in cell protection and tissue regeneration. A clue to the understanding of these contradictory biological phenomena may arise from recent findings which reveal a regulatory role of receptor internalization and intracellular receptor trafficking in selectively transmitting signals, which lead either to apoptosis or to the survival of the cell. In this chapter, we discuss the dichotomy of pro- and antiapoptotic signaling of the death receptors TNF-R1 and CD95. First, we will address the role of lipid rafts and post-translational modifications of death receptors in regulating the formation of receptor complexes. Then, we will discuss the role of internalization in determining the fate of the receptors and subsequently the specificity of signaling events. We propose that fusion of internalized TNF-receptosomes with trans-Golgi vesicles should be recognized as a novel mechanism to transduce death signals along the endocytic route. Finally, the lessons learnt from the strategy of adenovirus to escape apoptosis by targeting death receptor internalization demonstrate the biological significance of TNF receptor compartmentalization for immunosurveillance.
Artykov A, Yagolovich A, Dolgikh D, Kirpichnikov M, Trushina D, Gasparian M Front Cell Dev Biol. 2021; 9:733688.
PMID: 34660590 PMC: 8514705. DOI: 10.3389/fcell.2021.733688.
TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition.
Franco M, Garcia-Carpio I, Comaposada-Baro R, Escribano-Saiz J, Chavez-Gutierrez L, Vilar M Life Sci Alliance. 2021; 4(4).
PMID: 33536237 PMC: 7898468. DOI: 10.26508/lsa.202000844.
Dreschers S, Platen C, Ludwig A, Gille C, Kostlin N, Orlikowsky T Int J Mol Sci. 2019; 20(6).
PMID: 30897723 PMC: 6471605. DOI: 10.3390/ijms20061399.
Dreschers S, Gille C, Haas M, Seubert F, Platen C, Orlikowsky T PLoS One. 2017; 12(8):e0182415.
PMID: 28793310 PMC: 5549969. DOI: 10.1371/journal.pone.0182415.
Carotenuto F, Coletti D, Nardo P, Teodori L Eur J Transl Myol. 2017; 26(4):6033.
PMID: 28078067 PMC: 5220214. DOI: 10.4081/ejtm.2016.6033.