Endosomal “sort” of signaling control: The role of ESCRT machinery in regulation of receptor-mediated signaling pathways

Szymańska, Ewelina; Budick-Harmelin, Noga; Miączyńska, Marta

doi:10.1016/j.semcdb.2017.08.012

Cited by 43 publications

(38 citation statements)

References 98 publications

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“…Obviously, the limited ability to differentiate between these organelles at the light microscopy level has been a serious drawback for researchers in the field. A number of excellent recent reviews have addressed aspects of LEs that relate to degradation, autophagy and lysosomes Nakamura and Yoshimori, 2017;Pu et al, 2016;Scott et al, 2014;Szymanska et al, 2017), and, LEs will thus be addressed only briefly here, focusing on their relationship to other endosomes. Although it remains incompletely resolved whether endosomes actually 'mature' from an EE into a LE, or whether vesicles bud from EE and then transport cargo to a more static LE, there are a number of well-established differences between EEs and LEs.…”

Section: Late Endosomesmentioning

confidence: 99%

The enigmatic endosome – sorting the ins and outs of endocytic trafficking

Naslavsky

Caplan

2018

Journal of Cell Science

271

258

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The early endosome (EE), also known as the sorting endosome (SE) is a crucial station for the sorting of cargoes, such as receptors and lipids, through the endocytic pathways. The term endosome relates to the receptacle-like nature of this organelle, to which endocytosed cargoes are funneled upon internalization from the plasma membrane. Having been delivered by the fusion of internalized vesicles with the EE or SE, cargo molecules are then sorted to a variety of endocytic pathways, including the endo-lysosomal pathway for degradation, direct or rapid recycling to the plasma membrane, and to a slower recycling pathway that involves a specialized form of endosome known as a recycling endosome (RE), often localized to the perinuclear endocytic recycling compartment (ERC). It is striking that 'the endosome', which plays such essential cellular roles, has managed to avoid a precise description, and its characteristics remain ambiguous and heterogeneous. Moreover, despite the rapid advances in scientific methodologies, including breakthroughs in light microscopy, overall, the endosome remains poorly defined. This Review will attempt to collate key characteristics of the different types of endosomes and provide a platform for discussion of this unique and fascinating collection of organelles. Moreover, under-developed, poorly understood and important open questions will be discussed.

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Section: Late Endosomesmentioning

confidence: 99%

The enigmatic endosome – sorting the ins and outs of endocytic trafficking

Naslavsky

Caplan

2018

Journal of Cell Science

271

258

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“…Signaling receptors (mainly receptor tyrosine kinases) subject to degradation are marked by ubiquitination on lysine‐63 and are recognized by the evolutionarily conserved endosomal sorting complexes required for transport (ESCRT) machinery, which drives membrane deformation and vesicle scission to generate cargo‐enriched intraluminal vesicles . In theory, the ESCRT machinery should play an essential role in the degradation of metabolically active signaling receptors.…”

Section: The Role Of Endosomal Degradation In Metabolic Controlmentioning

confidence: 99%

Metabolic regulation through the endosomal system

Gilleron

Gerdes

Zeigerer

2019

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The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type 2 diabetes, hypercholesterolemia and non‐alcoholic fatty liver disease. By taking insights from in vitro studies of endocytosis and exploring their effects on metabolism, we can begin to connect the fields of endosomal transport and metabolic homeostasis. In this review, we explore current understanding of how the endosomal system influences the systemic regulation of glucose and lipid metabolism in mice and humans. We highlight exciting new insights that help translate findings from single cells to a wider physiological level and open up new directions for endosomal research.

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“…Endocytic internalization and trafficking can regulate the signal transduction of plasma membrane receptors in multiple ways. These include termination of signaling through lysosomal degradation of receptors but also maintenance of signaling by retention of active receptors on endosomes (Barbieri et al, 2016;Miaczynska, 2013;Szymanska et al, 2018;Villasenor et al, 2016). While our knowledge of mechanisms linking trafficking and signaling comes mostly from research on receptor tyrosine kinases or G proteincoupled receptors, less is known about cytokine receptors of the tumor necrosis factor receptor (TNFR) superfamily (Cendrowski et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The topology of the lymphotoxin β receptor that accumulates upon endolysosomal dysfunction dictates the NF-κB signaling outcome

Banach-Orlowska

Jastrzębski

Cendrowski

et al. 2018

Journal of Cell Science

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Cytokine receptors, such as tumor necrosis factor receptor I (TNFRI, also known as TNFRSF1A) and lymphotoxin β receptor (LTβR), activate inflammatory nuclear factor (NF)-κB signaling upon stimulation. We have previously demonstrated that depletion of ESCRT components leads to endosomal accumulation of TNFRI and LTβR, and their ligand-independent signaling to NF-κB. Here, we studied whether other perturbations of the endolysosomal system could trigger intracellular accumulation and signaling of ligand-free LTβR. While depletion of the CORVET components had no effect, knockdown of Rab7a or HOPS components, or pharmacological inhibition of lysosomal degradation, caused endosomal accumulation of LTβR and increased its interaction with the TRAF2 and TRAF3 signaling adaptors. However, the NF-κB pathway was not activated under these conditions. We found that knockdown of Rab7a or HOPS components led to sequestration of LTβR in intraluminal vesicles of endosomes, thus precluding NF-κB signaling. This was in contrast to the LTβR localization on the outer endosomal membrane that was seen after ESCRT depletion and was permissive for signaling. We propose that the inflammatory response induced by intracellular accumulation of endocytosed cytokine receptors critically depends on the precise receptor topology within endosomal compartments.

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Endosomal “sort” of signaling control: The role of ESCRT machinery in regulation of receptor-mediated signaling pathways

Cited by 43 publications

References 98 publications

The enigmatic endosome – sorting the ins and outs of endocytic trafficking

The enigmatic endosome – sorting the ins and outs of endocytic trafficking

Metabolic regulation through the endosomal system

The topology of the lymphotoxin β receptor that accumulates upon endolysosomal dysfunction dictates the NF-κB signaling outcome

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