scholarly journals Hrr25 triggers selective autophagy–related pathways by phosphorylating receptor proteins

2014 ◽  
Vol 207 (1) ◽  
pp. 91-105 ◽  
Author(s):  
Chikara Tanaka ◽  
Li-Jing Tan ◽  
Keisuke Mochida ◽  
Hiromi Kirisako ◽  
Michiko Koizumi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
Receptor Proteins ◽  
Selective Autophagy ◽  
The Core ◽  
The Common ◽  
Related Proteins

In selective autophagy, degradation targets are specifically recognized, sequestered by the autophagosome, and transported into the lysosome or vacuole. Previous studies delineated the molecular basis by which the autophagy machinery recognizes those targets, but the regulation of this process is still poorly understood. In this paper, we find that the highly conserved multifunctional kinase Hrr25 regulates two distinct selective autophagy–related pathways in Saccharomyces cerevisiae. Hrr25 is responsible for the phosphorylation of two receptor proteins: Atg19, which recognizes the assembly of vacuolar enzymes in the cytoplasm-to-vacuole targeting pathway, and Atg36, which recognizes superfluous peroxisomes in pexophagy. Hrr25-mediated phosphorylation enhances the interactions of these receptors with the common adaptor Atg11, which recruits the core autophagy-related proteins that mediate the formation of the autophagosomal membrane. Thus, this study introduces regulation of selective autophagy as a new role of Hrr25 and, together with other recent studies, reveals that different selective autophagy–related pathways are regulated by a uniform mechanism: phosphoregulation of the receptor–adaptor interaction.

Uptake and trafficking of exogenous sterols in Saccharomyces cerevisiae

2006 ◽  
Vol 34 (3) ◽  
pp. 359-362 ◽  
Author(s):  
S. Raychaudhuri ◽  
W.A. Prinz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Abc Transporters ◽  
Cellular Functions ◽  
Yeast Saccharomyces Cerevisiae ◽  
Membrane Function ◽  
Oxysterol Binding Protein ◽  
Atp Binding Cassette Transporters ◽  
Related Proteins

The proper distribution of sterols among organelles is critical for numerous cellular functions. How sterols are sorted and moved among membranes remains poorly understood, but they are transported not only in vesicles but also by non-vesicular pathways. One of these pathways moves exogenous sterols from the plasma membrane to the endoplasmic reticulum in the yeast Saccharomyces cerevisiae. We have found that two classes of proteins play critical roles in this transport, ABC transporters (ATP-binding-cassette transporters) and oxysterol-binding protein-related proteins. Transport is also regulated by phosphoinositides and the interactions of sterols with other lipids. Here, we summarize these findings and speculate on the role of non-vesicular sterol transfer in determining intracellular sterol distribution and membrane function.

scholarly journals A Role for Gcn5-Mediated Global Histone Acetylation in Transcriptional Regulation

2006 ◽  
Vol 26 (5) ◽  
pp. 1610-1616 ◽  
Author(s):  
Rachel Maria Imoberdorf ◽  
Irini Topalidou ◽  
Michel Strubin
Keyword(s):  
Histone Acetylation ◽  
Core Promoter ◽  
Histone Acetyltransferases ◽  
Gene Promoters ◽  
Core Promoters ◽  
The Core ◽  
Strength Of Interaction ◽  
Genome Wide ◽  
The Common

ABSTRACT Transcriptional activators often require histone acetyltransferases (HATs) for full activity. The common explanation is that activators directly recruit HATs to gene promoters to locally hyperacetylate histones and thereby facilitate transcription complex formation. However, in addition to being targeted to specific loci, HATs such as Gcn5 also modify histones genome-wide. Here we provide evidence for a role of this global HAT activity in regulated transcription. We show that activation by direct recruitment of the transcriptional machinery neither recruits Gcn5 nor induces changes in histone acetylation yet can strongly depend on Gcn5 at promoters showing a high basal state of Gcn5-mediated histone acetylation. We also show that Gcn5 dependency varies among core promoters and is influenced by the strength of interaction used to recruit the machinery and by the affinity of the latter for the core promoter. These data support a role for global Gcn5 HAT activity in modulating transcription independently of its known coactivator function.

scholarly journals Autophagy in Neurons

2019 ◽  
Vol 35 (1) ◽  
pp. 477-500 ◽  
Author(s):  
Andrea K.H. Stavoe ◽  
Erika L.F. Holzbaur
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Biology ◽  
Neuronal Development ◽  
Selective Autophagy ◽  
The Core ◽  
Differentiated Cells ◽  
Neuronal Homeostasis ◽  
Core Components ◽  
Cellular Organelles

Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. Autophagy is particularly important in neurons, which are terminally differentiated cells that must last the lifetime of the organism. There are both constitutive and stress-induced pathways for autophagy in neurons, which catalyze the turnover of aged or damaged mitochondria, endoplasmic reticulum, other cellular organelles, and aggregated proteins. These pathways are required in neurodevelopment as well as in the maintenance of neuronal homeostasis. Here we review the core components of the pathway for autophagosome biogenesis, as well as the cell biology of bulk and selective autophagy in neurons. Finally, we discuss the role of autophagy in neuronal development, homeostasis, and aging and the links between deficits in autophagy and neurodegeneration.

scholarly journals The molecular basis of IL-21–mediated proliferation

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4135-4142 ◽  
Author(s):  
Rong Zeng ◽  
Rosanne Spolski ◽  
Esther Casas ◽  
Wei Zhu ◽  
David E. Levy ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Severe Combined Immunodeficiency ◽  
Type I ◽  
Combined Immunodeficiency ◽  
Knock Out ◽  
Tyrosine Residues ◽  
The Common ◽  
Knock Out Mice ◽  
Β Chain

AbstractInterleukin-21 (IL-21) is a type I cytokine that modulates functions of T, B, natural killer (NK), and myeloid cells. The IL-21 receptor (IL-21R) is closely related to the IL-2 receptor β chain and is capable of transducing signals through its dimerization with the common cytokine receptor γ chain (γc), the protein whose expression is defective in humans with X-linked severe combined immunodeficiency. To clarify the molecular basis of IL-21 actions, we investigated the role of tyrosine residues in the IL-21R cytoplasmic domain. Simultaneous mutation of all 6 tyrosines greatly diminished IL-21–mediated proliferation, whereas retention of tyrosine 510 (Y510) allowed full proliferation. Y510 efficiently mediated IL-21–induced phosphorylation of Stat1 and Stat3, but not of Stat5, and CD8+ T cells from Stat1/Stat3 double knock-out mice exhibited decreased proliferation in response to IL-21 + IL-15. In addition, IL-21 weakly induced phosphorylation of Shc and Akt, and consistent with this, specific inhibitors of the MAPK and PI3K pathways inhibited IL-21–mediated proliferation. Collectively, these data indicate the involvement of the Jak-STAT, MAPK, and PI3K pathways in IL-21 signaling.

scholarly journals Yeast R2TP Interacts with Extended Termini of Client Protein Nop58p

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ge Yu ◽  
Yu Zhao ◽  
Shaoxiong Tian ◽  
Jay Rai ◽  
Huan He ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Maltose Binding Protein ◽  
Small Subunit ◽  
General Mechanism ◽  
Yeast Genetics ◽  
Client Protein ◽  
Present Evidence ◽  
Aaa Atpase ◽  
The Core

AbstractThe AAA + ATPase R2TP complex facilitates assembly of a number of ribonucleoprotein particles (RNPs). Although the architecture of R2TP is known, its molecular basis for acting upon multiple RNPs remains unknown. In yeast, the core subunit of the box C/D small nucleolar RNPs, Nop58p, is the target for R2TP function. In the recently observed U3 box C/D snoRNP as part of the 90 S small subunit processome, the unfolded regions of Nop58p are observed to form extensive interactions, suggesting a possible role of R2TP in stabilizing the unfolded region of Nop58p prior to its assembly. Here, we analyze the interaction between R2TP and a Maltose Binding Protein (MBP)-fused Nop58p by biophysical and yeast genetics methods. We present evidence that R2TP interacts largely with the unfolded termini of Nop58p. Our results suggest a general mechanism for R2TP to impart specificity by recognizing unfolded regions in its clients.

scholarly journals Ubiquitin-Mediated Regulation of Endocytosis by Proteins of the Arrestin Family

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Michel Becuwe ◽  
Antonio Herrador ◽  
Rosine Haguenauer-Tsapis ◽  
Olivier Vincent ◽  
Sébastien Léon
Keyword(s):  
Ubiquitin Ligase ◽  
Adaptor Proteins ◽  
Receptor Trafficking ◽  
G Protein Coupled Receptors ◽  
Endocytic Pathway ◽  
Ubiquitin Pathway ◽  
The Core ◽  
Related Proteins ◽  
G Protein Coupled

In metazoans, proteins of the arrestin family are key players of G-protein-coupled receptors (GPCRS) signaling and trafficking. Following stimulation, activated receptors are phosphorylated, thus allowing the binding of arrestins and hence an “arrest” of receptor signaling. Arrestins act by uncoupling receptors from G proteins and contribute to the recruitment of endocytic proteins, such as clathrin, to direct receptor trafficking into the endocytic pathway. Arrestins also serve as adaptor proteins by promoting the recruitment of ubiquitin ligases and participate in the agonist-induced ubiquitylation of receptors, known to have impact on their subcellular localization and stability. Recently, the arrestin family has expanded following the discovery of arrestin-related proteins in other eukaryotes such as yeasts or fungi. Surprisingly, most of these proteins are also involved in the ubiquitylation and endocytosis of plasma membrane proteins, thus suggesting that the role of arrestins as ubiquitin ligase adaptors is at the core of these proteins' functions. Importantly, arrestins are themselves ubiquitylated, and this modification is crucial for their function. In this paper, we discuss recent data on the intricate connections between arrestins and the ubiquitin pathway in the control of endocytosis.

Analysis of Reactor Magnetic Circuit Based on ANSYS Command Flow

2011 ◽  
Vol 383-390 ◽  
pp. 2256-2261
Author(s):  
Po Yang ◽  
Zhong Dong Yin ◽  
Ruo Chen Cui ◽  
Ning Kong
Keyword(s):  
Graphical User Interface ◽  
Structural Design ◽  
Reactive Power ◽  
Magnetic Circuit ◽  
Element Analysis ◽  
The Core ◽  
The Common ◽  
Controllable Reactor ◽  
The Magnetic Field

Controllable reactor is the common equipment in the modern power system, which plays an important role in voltage control and reactive power compensation. The core structure of reactor effects the magnetic field distribution in the core and the loss of reactor. In this paper, the models of two kinds of classic reactors are built by the ANSYS command flow method, and explain the differences between magnetic valve controllable reactor and common reactor. This paper points out the advantages of command flow compared with the graphical user interface and the important role of ANSYS finite element analysis in the structural design of reactor.

scholarly journals Structure of an endogenous yeast 26S proteasome reveals two major conformational states

2016 ◽  
Vol 113 (10) ◽  
pp. 2642-2647 ◽  
Author(s):  
Bai Luan ◽  
Xiuliang Huang ◽  
Jianping Wu ◽  
Ziqing Mei ◽  
Yiwei Wang ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Enzyme Activity ◽  
Molecular Basis ◽  
Biochemical Analysis ◽  
26S Proteasome ◽  
Core Particle ◽  
Conformational States ◽  
The Core ◽  
Substrate Structure ◽  
Exogenous Substrate

The eukaryotic proteasome mediates degradation of polyubiquitinated proteins. Here we report the single-particle cryoelectron microscopy (cryo-EM) structures of the endogenous 26S proteasome from Saccharomyces cerevisiae at 4.6- to 6.3-Å resolution. The fine features of the cryo-EM maps allow modeling of 18 subunits in the regulatory particle and 28 in the core particle. The proteasome exhibits two distinct conformational states, designated M1 and M2, which correspond to those reported previously for the proteasome purified in the presence of ATP-γS and ATP, respectively. These conformations also correspond to those of the proteasome in the presence and absence of exogenous substrate. Structure-guided biochemical analysis reveals enhanced deubiquitylating enzyme activity of Rpn11 upon assembly of the lid. Our structures serve as a molecular basis for mechanistic understanding of proteasome function.

The Ordeal of Incongruity

2020 ◽  
pp. 109-148
Author(s):  
Sam Gill
Keyword(s):  
Religious Experience ◽  
Personal Experience ◽  
The Core ◽  
The Common ◽  
Common Understanding ◽  
Written Description ◽  
Core Role

By contrasting his own personal experience dancing with Smith’s preference for reading, the author engages a complex and far-reaching discussion of the role and importance of experience both in religious subjects studied and in the lives of the scholars. From a biologically and philosophically based theory of experience, the chapter examines the importance of repetition, feeling kinds of knowing, and gesture, among other aspects of being bodied, to posit that religion and also the study of religion are skills honed through long repetitive experience. The chapter also engages the implications that sensory-rich religious experience is transduced into written description that is often the only access scholars have to their subjects of study. Countering the common understanding that Smith is reluctant to value experience, the chapter shows that the core role of incongruity and difference Smith attributes to religion and its study amounts to, in his own terms, an ordeal or determining experience.

scholarly journals Fission yeast Opy1 is an endogenous PI(4,5)P2 sensor that binds to the phosphatidylinositol 4-phosphate 5-kinase Its3

2020 ◽  
Vol 133 (23) ◽  
pp. jcs247973
Author(s):  
Chloe E. Snider ◽  
Alaina H. Willet ◽  
HannahSofia T. Brown ◽  
Jun-Song Chen ◽  
Joshua M. Evers ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Cell Biology ◽  
Kinase Activity ◽  
Striking Difference ◽  
Evolutionary Divergence ◽  
Ph Domain ◽  
Phosphatidylinositol 4 ◽  
Related Proteins

ABSTRACTPhosphoinositides (PIPs) are a dynamic family of lipids that execute diverse roles in cell biology. PIP levels are regulated by numerous enzymes, but our understanding of how these enzymes are controlled in space and time is incomplete. One role of the PIP phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is to anchor the cytokinetic ring (CR) to the plasma membrane (PM) in Schizosaccharomyces pombe. While examining potential PI(4,5)P2-binding proteins for roles in CR anchoring, we identified the dual pleckstrin homology (PH) domain-containing protein Opy1. Although related proteins are implicated in PIP regulation, we found no role for S. pombe Opy1 in CR anchoring, which would be expected if it modulated PM PI(4,5)P2 levels. Our data indicate that although Opy1 senses PM PI(4,5)P2 levels and binds to the phosphatidylinositol 4-phosphate 5-kinase (PI5-kinase) Its3, Opy1 does not regulate Its3 kinase activity or PM PI(4,5)P2 levels, a striking difference from its Saccharomyces cerevisiae homolog. However, overexpression of Opy1 resulted in cytokinesis defects, as might be expected if it sequestered PI(4,5)P2. Our results highlight the evolutionary divergence of dual PH domain-containing proteins and the need for caution when interpreting results based on their overexpression.This article has an associated First Person interview with the first author of the paper.

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