LTBR

Case study 1: Małgorzata Maksymowicz, 2020

At the cellular level, upon ligand binding, the receptor activates the pro-inflammatory NF-κB and AP-1 pathways. Yet, the intracellular distribution of LTβR, the routes of its endocytosis and their connection to the signaling activation are not characterized. Here, the researchers investigated the contribution of LTβR internalization to its signaling potential.

Intracellular localization of LTβR in unstimulated and stimulated cells was analyzed by confocal microscopy. Endocytosis impairment was achieved through siRNA- or CRISPR/Cas9-mediated depletion, or chemical inhibition of proteins regulating endocytic routes. The activation of LTβR-induced signaling was examined. A transcriptional response to LTβR stimulation was assessed by qRT-PCR analysis. The results showed that LTβR was predominantly present on endocytic vesicles and the Golgi apparatus. Depletion of regulators of different endocytic routes (clathrin-mediated, dynamin-dependent or clathrin-independent) resulted in the impairment of LTβR internalization, indicating that this receptor uses multiple entry pathways. This work shows that the impairment of clathrin- and dynamin-dependent internalization amplifies a cellular response to LTβR stimulation.

Fig1. A549 cells were stimulated with Ago for the indicated time periods and immunostained for LTβR, trans- (TGN46) and cis-Golgi (GM130).

Fig2. Lysates of A549 cells stimulated with: Ago, LTα1β2 and LIGHT for different time periods were analyzed by Western blotting with antibodies against the indicated proteins to assess activity of the NF-κB pathway.

Case study 2: Magdalena Banach-Orłowska, 2018

The researchers previously demonstrated that depletion of ESCRT components leads to endosomal accumulation of TNFRI and LTβR, and their ligand-independent signaling to NF-κB. Here, they studied if other perturbations of the endolysosomal system could trigger intracellular accumulation and signaling of ligand-free LTβR.

While depletion of CORVET had no effect, knockdown of HOPS or Rab7, or pharmacological inhibition of lysosomal degradation, caused endosomal accumulation of LTβR and its increased interactions with TRAF2/TRAF3 signaling adaptors. And the LTβR sequestration in intraluminal vesicles of endosomes precluded NF-κB signaling. Sequestration of LTβR in intraluminal vesicles of endosomes upon depletion of HOPS components or Rab7 precludes NF-κB signaling, whereas LTβR accumulation on the outer endosomal membrane after ESCRT depletion promotes signaling.

Fig3. Immunofluorescence staining of LTβR, EEA1 and LAMP1 in HeLa cells upon knockdown of Vps16 or Vps18 and in control (Ctrl) siRNA-transfected cells.

Fig4. (Left panel) Western blot analysis of immunoprecipitation (IP) of LTβR in extracts of HeLa cells transfected with non-targeting (Ctrl) or Rab7- and Vps11-targeting siRNA.

LTBR involved in several pathways and played different roles in them. We selected most pathways LTBR participated on our site, such as Cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, HIF- signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with LTBR were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

LTBR has several biochemical functions, for example, identical protein binding, protein binding, tumor necrosis factor-activated receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by LTBR itself. We selected most functions LTBR had, and list some proteins which have the same functions with LTBR. You can find most of the proteins on our site.

LTBR has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with LTBR here. Most of them are supplied by our site. Hope this information will be useful for your research of LTBR.

p29846-pro_0000037666; ZMYND11; DEAF1; TRAF2; TRAF3; BALF4 (provisional); HES1; q00653-pro_000003032; Bmpr1a; NFKB2

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