23 research outputs found
NRP/Optineurin Cooperates with TAX1BP1 to Potentiate the Activation of NF-κB by Human T-Lymphotropic Virus Type 1 Tax Protein
Nuclear factor (NF)-κB is a major survival pathway engaged by the Human T-Lymphotropic Virus type 1 (HTLV-1) Tax protein. Tax1 activation of NF-κB occurs predominantly in the cytoplasm, where Tax1 binds NF-κB Essential Modulator (NEMO/IKKγ) and triggers the activation of IκB kinases. Several independent studies have shown that Tax1-mediated NF-κB activation is dependent on Tax1 ubiquitination. Here, we identify by co-immunoprecipitation assays NEMO-Related Protein (NRP/Optineurin) as a binding partner for Tax1 in HTLV-1 infected and Tax1/NRP co-expressing cells. Immunofluorescence studies reveal that Tax1, NRP and NEMO colocalize in Golgi-associated structures. The interaction between Tax1 and NRP requires the ubiquitin-binding activity of NRP and the ubiquitination sites of Tax1. In addition, we observe that NRP increases the ubiquitination of Tax1 along with Tax1-dependent NF-κB signaling. Surprisingly, we find that in addition to Tax1, NRP interacts cooperatively with the Tax1 binding protein TAX1BP1, and that NRP and TAX1BP1 cooperate to modulate Tax1 ubiquitination and NF-κB activation. Our data strongly suggest for the first time that NRP is a critical adaptor that regulates the assembly of TAX1BP1 and post-translationally modified forms of Tax1, leading to sustained NF-κB activation
Sources of mycosporine-like amino acids in planktonic Chlorella-bearing ciliates (Ciliophora)
Mycosporine-like amino acids (MAAs) are a family of secondary metabolites known to protect organisms exposed to solar UV radiation. We tested their distribution among several planktonic ciliates bearing Chlorella isolated from an oligo-mesotrophic lake in Tyrol, Austria. In order to test the origin of these compounds, the MAAs were assessed by high performance liquid chromatography in both the ciliates and their symbiotic algae.Considering all Chlorella-bearing ciliates, we found: (i) seven different MAAs (mycosporine-glycine, palythine, asterina-330, shinorine, porphyra-334, usujirene, palythene); (ii) one to several MAAs per species and (iii) qualitative and quantitative seasonal changes in the MAAs (e.g. in Pelagodileptus trachelioides). In all species tested, concentrations of MAAs were always <1% of ciliate dry weight.Several MAAs were also identified in the Chlorella isolated from the ciliates, thus providing initial evidence for their symbiotic origin. In Uroleptus sp., however, we found evidence for a dietary source of MAAs.Our results suggest that accumulation of MAAs in Chlorella-bearing ciliates represents an additional benefit of this symbiosis and an adaptation for survival in sunlit, UV-exposed waters
Integrin α5β1 Function Is Regulated by XGIPC/kermit2 Mediated Endocytosis during Xenopus laevis Gastrulation
During Xenopus gastrulation α5β1 integrin function is modulated in a temporally and spatially restricted manner, however, the regulatory mechanisms behind this regulation remain uncharacterized. Here we report that XGIPC/kermit2 binds to the cytoplasmic domain of the α5 subunit and regulates the activity of α5β1 integrin. The interaction of kermit2 with α5β1 is essential for fibronectin (FN) matrix assembly during the early stages of gastrulation. We further demonstrate that kermit2 regulates α5β1 integrin endocytosis downstream of activin signaling. Inhibition of kermit2 function impairs cell migration but not adhesion to FN substrates indicating that integrin recycling is essential for mesoderm cell migration. Furthermore, we find that the α5β1 integrin is colocalized with kermit2 and Rab 21 in embryonic and XTC cells. These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the α5β1 integrin through receptor endocytosis