scholarly journals SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways

2012 ◽  
Vol 197 (2) ◽  
pp. 219-230 ◽  
Author(s):  
Florian Steinberg ◽  
Kate J. Heesom ◽  
Mark D. Bass ◽  
Peter J. Cullen
Keyword(s):  
Isotope Labeling ◽  
Degradation Pathway ◽  
Lysosomal Degradation ◽  
Sorting Nexins ◽  
Retromer Complex ◽  
Proteomic Approach ◽  
Cytoplasmic Tails ◽  
Npxy Motif ◽  
Global Identification ◽  
Insight Into

The FERM-like domain–containing sorting nexins of the SNX17/SNX27/SNX31 family have been proposed to mediate retrieval of transmembrane proteins from the lysosomal pathway. In this paper, we describe a stable isotope labeling with amino acids in culture–based quantitative proteomic approach that allows an unbiased, global identification of transmembrane cargoes that are rescued from lysosomal degradation by SNX17. This screen revealed that several integrins required SNX17 for their stability, as depletion of SNX17 led to a loss of β1 and β5 integrins and associated a subunits from HeLa cells as a result of increased lysosomal degradation. SNX17 bound to the membrane distal NPXY motif in β integrin cytoplasmic tails, thereby preventing lysosomal degradation of β integrins and their associated a subunits. Furthermore, SNX17-dependent retrieval of integrins did not depend on the retromer complex. Consistent with an effect on integrin recycling, depletion of SNX17 also caused alterations in cell migration. Our data provide mechanistic insight into the retrieval of internalized integrins from the lysosomal degradation pathway, a prerequisite for subsequent recycling of these matrix receptors.

scholarly journals Autophagy gene-dependent intracellular immunity triggered by interferon-γ

2021 ◽  
Author(s):  
Michael R McAllaster ◽  
Jaya Bhushan ◽  
Dale R Balce ◽  
Anthony Orvedahl ◽  
Arnold Park ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Interferon Γ ◽  
Degradation Pathway ◽  
Lysosomal Degradation ◽  
Cellular Processes ◽  
Binding Domains ◽  
New Genes ◽  
Autophagy Gene ◽  
Atg Genes ◽  
Dependent Processes

Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of Norovirus and Toxoplasma gondii replication. Herein we identified new genes that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. IFNγ-induced inhibition of norovirus replication required Wipi2b and Atg9a, but not Becn1 (encoding Beclin1), Atg14, or Sqstm1. The phosphatidylinositol-3-phosphate and ATG16L1 binding domains of WIPI2B were required for IFNγ-induced inhibition of norovirus replication. Both WIPI2 and SQSTM1 were required for IFN?-induced inhibition of Toxoplasma gondii replication in HeLa cells. These studies further delineate the mechanisms of a programmable form of cytokine-induced intracellular immunity that relies on an expanding cassette of essential ATG genes to restrict the growth of phylogenetically diverse pathogens.

scholarly journals Poly(A) tail shortening is the translation-dependent step in c-myc mRNA degradation.

1990 ◽  
Vol 10 (12) ◽  
pp. 6132-6140 ◽  
Author(s):  
I A Laird-Offringa ◽  
C L de Wit ◽  
P Elfferich ◽  
A J van der Eb
Keyword(s):  
Protein Synthesis ◽  
Actinomycin D ◽  
Degradation Pathway ◽  
Mrna Degradation ◽  
The Body ◽  
Second Step ◽  
Protein Synthesis Inhibitors ◽  
Rapid Degradation ◽  
Translation Block ◽  
Insight Into

The highly unstable c-myc mRNA has been shown to be stabilized in cells treated with protein synthesis inhibitors. We have studied this phenomenon in an effort to gain more insight into the degradation pathway of this mRNA. Our results indicate that the stabilization of c-myc mRNA in the absence of translation can be fully explained by the inhibition of translation-dependent poly(A) tail shortening. This view is based on the following observations. First, the normally rapid shortening of the c-myc poly(A) tail was slowed down by a translation block. Second, c-myc messengers which carry a short poly(A) tail, as a result of prolonged actinomycin D or 3'-deoxyadenosine treatment, were not stabilized by the inhibition of translation. We propose that c-myc mRNA degradation proceeds in at least two steps. The first step is the shortening of long poly(A) tails. This step requires ongoing translation and thus is responsible for the delay in mRNA degradation observed in the presence of protein synthesis inhibitors. The second step involves rapid degradation of the body of the mRNA, possibly preceded by the removal of the short remainder of the poly(A) tail. This last step is independent of translation.

scholarly journals Revealing the fate of cell surface human P-glycoprotein (ABCB1): The lysosomal degradation pathway

2015 ◽  
Vol 1853 (10) ◽  
pp. 2361-2370 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Khyati Kapoor ◽  
Shinobu Ohnuma ◽  
Atish Patel ◽  
William Swaim ◽  
...  
Keyword(s):  
Cell Surface ◽  
Degradation Pathway ◽  
Lysosomal Degradation ◽  
P Glycoprotein

scholarly journals An Intervention Target for Myocardial Fibrosis: Autophagy

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Chunmiao Lu ◽  
Yusong Yang ◽  
Yaping Zhu ◽  
Shichao Lv ◽  
Junping Zhang
Keyword(s):  
Cardiovascular Diseases ◽  
Myocardial Fibrosis ◽  
Collagen Synthesis ◽  
Degradation Pathway ◽  
Lysosomal Degradation ◽  
Metabolic Imbalance

Myocardial fibrosis (MF) is the result of metabolic imbalance of collagen synthesis and metabolism, which is widespread in various cardiovascular diseases. Autophagy is a lysosomal degradation pathway which is highly conserved. In recent years, research on autophagy has been increasing and the researchers have also become cumulatively aware of the specified association between autophagy and MF. This review highlights the role of autophagy in MF and the potential effects through the administration of medicine.

scholarly journals NUMB regulates the endocytosis and activity of the anaplastic lymphoma kinase in an isoform-specific manner

2019 ◽  
Vol 11 (11) ◽  
pp. 994-1005 ◽  
Author(s):  
Ran Wei ◽  
Xuguang Liu ◽  
Courtney Voss ◽  
Wentao Qin ◽  
Lina Dagnino ◽  
...  
Keyword(s):  
Cell Fate ◽  
Receptor Tyrosine Kinase ◽  
Anaplastic Lymphoma Kinase ◽  
Degradation Pathway ◽  
Anaplastic Lymphoma ◽  
Mechanistic Insight ◽  
Evolutionarily Conserved ◽  
Specific Manner ◽  
Insight Into

Abstract NUMB is an evolutionarily conserved protein that plays an important role in cell adhesion, migration, polarity, and cell fate determination. It has also been shown to play a role in the pathogenesis of certain cancers, although it remains controversial whether NUMB functions as an oncoprotein or tumor suppressor. Here, we show that NUMB binds to anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase aberrantly activated in several forms of cancer, and this interaction regulates the endocytosis and activity of ALK. Intriguingly, the function of the NUMB–ALK interaction is isoform-dependent. While both p66-NUMB and p72-NUMB isoforms are capable of mediating the endocytosis of ALK, the former directs ALK to the lysosomal degradation pathway, thus decreasing the overall ALK level and the downstream MAP kinase signal. In contrast, the p72-NUMB isoform promotes ALK recycling back to the plasma membrane, thereby maintaining the kinase in its active state. Our work sheds light on the controversial role of different isoforms of NUMB in tumorigenesis and provides mechanistic insight into ALK regulation.

Sorting nexins, a component of retromer complex, interact with SRK in Brassica oleracea

2020 ◽  
Vol 42 (1) ◽  
Author(s):  
Jing Zeng ◽  
Xiaoping Lian ◽  
Yan-ling Mo ◽  
Jingjing Chen ◽  
Yihua Liu ◽  
...  
Keyword(s):  
Brassica Oleracea ◽  
Sorting Nexins ◽  
Retromer Complex

scholarly journals Autophagy Modulation in Lymphocytes From COVID-19 Patients: New Therapeutic Target in SARS-COV-2 Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Marta Vomero ◽  
Cristiana Barbati ◽  
Tania Colasanti ◽  
Alessandra Ida Celia ◽  
Mariangela Speziali ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Degradation Pathway ◽  
The Novel ◽  
Lysosomal Degradation ◽  
Tnf Α ◽  
Evolutionarily Conserved ◽  
Novel Coronavirus ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the “cytokine storm.” Among these, interleukin (IL)-6, tumor necrosis factor‐α (TNF‐α), and IL-1β seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNF‐α, and IL-1β in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection.

Insight into the biological pathways underlying fibromyalgia by a proteomic approach

2018 ◽  
Vol 186 ◽  
pp. 47-55 ◽  
Author(s):  
Jorge A. Ramírez-Tejero ◽  
Esther Martínez-Lara ◽  
Alma Rus ◽  
María Victoria Camacho ◽  
María Luisa Del Moral ◽  
...  
Keyword(s):  
Biological Pathways ◽  
Proteomic Approach ◽  
Insight Into

scholarly journals Molecular cloning of disintegrins from Cerastes vipera and Macrovipera lebetina transmediterranea venom gland cDNA libraries: insight into the evolution of the snake venom integrin-inhibition system

2006 ◽  
Vol 395 (2) ◽  
pp. 385-392 ◽  
Author(s):  
Libia Sanz ◽  
Amine Bazaa ◽  
Naziha Marrakchi ◽  
Alicia Pérez ◽  
Mehdi Chenik ◽  
...  
Keyword(s):  
Snake Venom ◽  
Binding Sites ◽  
Venom Gland ◽  
Cdna Libraries ◽  
Common Ancestry ◽  
Integrin Receptors ◽  
Proteomic Approach ◽  
Ligand Binding Sites ◽  
Insight Into ◽  
Laminin Binding

We report the cloning and sequence analysis of Cerastes vipera and Macrovipera lebetina transmediterranea cDNAs coding for short non-RGD (Arg-Gly-Asp) disintegrins and for dimeric disintegrin subunits. The mRNAs belong to the short-coding class, suggesting that these disintegrin mRNAs may be more widely distributed than previously thought. Our data also argue for a common ancestry of the mRNAs of short disintegrins and those coding for precursors of dimeric disintegrin chains. The Macrovipera lebetina transmediterranea dimeric disintegrin reported to inhibit the laminin-binding integrins α3β1, α6β1 and α7β1 was analysed using a proteomic approach and was shown to bear MLD (Met-Leu-Asp) and VGD (Val-Gly-Asp) motifs. The results highlight the fact that disintegrins have evolved a restricted panel of integrin-blocking sequences that segregate with defined branches of the phylogenetic tree of the integrin α-chains, providing novel insights into the evolutionary adaptation of the snake venom antagonists to the ligand-binding sites of their target integrin receptors.

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