S100A13 and S100A6 exhibit distinct translocation pathways in endothelial cells

2002 ◽  
Vol 115 (15) ◽  
pp. 3149-3158 ◽  
Author(s):  
Hsiao-Ling Hsieh ◽  
Beat W. Schäfer ◽  
Jos A. Cox ◽  
Claus W. Heizmann
Keyword(s):  
Endothelial Cells ◽  
Calcium Binding ◽  
Protein Translocation ◽  
S100 Proteins ◽  
Cellular Functions ◽  
Specific Expression ◽  
Binding Domains ◽  
Cellular Environment ◽  
Ef Hands ◽  
Physiological Tasks

S100 proteins have attracted great interest in recent years because of their cell- and tissue-specific expression and association with various human pathologies. Most S100 proteins are small acidic proteins with calcium-binding domains — the EF hands. It is thought that this group of proteins carry out their cellular functions by interacting with specific target proteins, an interaction that is mainly dependent on exposure of hydrophobic patches, which result from calcium binding. S100A13, one of the most recently identified members of the S100 family, is expressed in various tissues. Interestingly,hydrophobic exposure was not observed upon calcium binding to S100A13 even though the dimeric form displays two high- and two low- affinity sites for calcium. Here, we followed the translocation of S100A13 in response to an increase in intracellular calcium levels, as protein translocation has been implicated in assembly of signaling complexes and signaling cascades, and several other S100 proteins are involved in such events. Translocation of S100A13 was observed in endothelial cells in response to angiotensin II, and the process was dependent on the classic Golgi-ER pathway. By contrast, S100A6 translocation was found to be distinct and dependent on actin-stress fibers. These experiments suggest that different S100 proteins utilize distinct translocation pathways, which might lead them to certain subcellular compartments in order to perform their physiological tasks in the same cellular environment.

scholarly journals Signal Inhibitory Receptor on Leukocytes-1 recognizes S100 proteins

2021 ◽  
Author(s):  
Matevž Rumpret ◽  
Helen J. von Richthofen ◽  
Maarten van der Linden ◽  
Geertje H. A. Westerlaken ◽  
Cami Talavera Ormeño ◽  
...  
Keyword(s):  
Calcium Binding ◽  
S100 Protein ◽  
S100 Proteins ◽  
Human Neutrophils ◽  
Ros Production ◽  
Inhibitory Receptor ◽  
Binding Domains ◽  
Activating Receptors ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Signal inhibitory receptor on leukocytes-1 (SIRL-1) is an inhibitory receptor with a hitherto unknown ligand, and is expressed on human monocytes and neutrophils. SIRL-1 inhibits myeloid effector functions such as reactive oxygen species (ROS) production. We here identify S100 proteins as SIRL-1 ligands. S100 proteins are composed of two calcium-binding domains. Various S100 proteins are damage-associated molecular patterns (DAMPs) released from damaged cells, after which they initiate inflammation by ligating activating receptors on immune cells. We now show that the inhibitory SIRL-1 recognizes individual calcium-binding domains of all tested S100 proteins. Blocking SIRL-1 on human neutrophils enhanced S100 protein S100A6-induced ROS production, showing that S100A6 suppresses neutrophil ROS production via SIRL-1. We conclude that SIRL-1 is an inhibitory receptor recognizing the S100 protein family of DAMPs.

scholarly journals The AAA+ ATPase p97, a cellular multitool

2017 ◽  
Vol 474 (17) ◽  
pp. 2953-2976 ◽  
Author(s):  
Lasse Stach ◽  
Paul S. Freemont
Keyword(s):  
Atp Hydrolysis ◽  
Current Status ◽  
Cellular Functions ◽  
Aaa Atpase ◽  
Cellular Processes ◽  
Proteotoxic Stress ◽  
Binding Domains ◽  
Wide Range ◽  
Aaa Atpases ◽  
Substrate Proteins

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy.

scholarly journals Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription Factors

2006 ◽  
Vol 17 (2) ◽  
pp. 585-597 ◽  
Author(s):  
Fang Liu ◽  
Nabendu Pore ◽  
Mijin Kim ◽  
K. Ranh Voong ◽  
Melissa Dowling ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Sequences ◽  
Chromatin Immunoprecipitation ◽  
Histone Deacetylases ◽  
Targeted Mutagenesis ◽  
Cellular Functions ◽  
Specific Expression ◽  
Protein Levels ◽  
Histone Deacetylase 4 ◽  
First Time

Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA sequences. We validated consensus binding sites for Sp1/Sp3 transcription factors in the HDAC4 promoter through truncation studies and targeted mutagenesis. Specific and functional binding by Sp1/Sp3 at these sites was confirmed with chromatin immunoprecipitation (ChIP) and electromobility shift assays (EMSA). Cotransfection of either Sp1 or Sp3 with a reporter driven by the HDAC4 promoter led to high activities in SL2 insect cells (which lack endogenous Sp1/Sp3). In human cells, restored expression of Sp1 and Sp3 up-regulated HDAC4 protein levels, whereas levels were decreased by RNA-interference-mediated knockdown of either protein. Finally, variable levels of Sp1 were in concordance with that of HDAC4 in a number of human tissues and cancer cell lines. These studies together characterize for the first time the activity of the HDAC4 promoter, through which Sp1 and Sp3 modulates expression of HDAC4 and which may contribute to tissue or cell-line-specific expression of HDAC4.

scholarly journals Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

2019 ◽  
Vol 116 (18) ◽  
pp. 8909-8918 ◽  
Author(s):  
Shinju Sugiyama ◽  
Motomasa Tanaka
Keyword(s):  
Wall Stress ◽  
Cell Periphery ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Binding Domains ◽  
Peripheral Proteins ◽  
Flow Through ◽  
Membrane Spanning ◽  
Mother Cells ◽  
Er Membrane

Protein segregation contributes to various cellular processes such as polarization, differentiation, and aging. However, the difficulty in global determination of protein segregation hampers our understanding of its mechanisms and physiological roles. Here, by developing a quantitative proteomics technique, we globally monitored segregation of preexisting and newly synthesized proteins during cell division of budding yeast, and identified crucial domains that determine the segregation of cell-peripheral proteins. Remarkably, the proteomic and subsequent microscopic analyses demonstrated that the flow through the bud neck of the proteins that harbor both endoplasmic reticulum (ER) membrane-spanning and plasma membrane (PM)-binding domains is not restricted by the previously suggested ER membrane or PM diffusion barriers but by septin-mediated partitioning of the PM-associated ER (pmaER). Furthermore, the proteomic analysis revealed that although the PM-spanning t-SNARE Sso2 was retained in mother cells, its paralog Sso1 unexpectedly showed symmetric localization. We found that the transport of Sso1 to buds was required for enhancement of polarized cell growth and resistance to cell-wall stress. Taken together, these data resolve long-standing questions about septin-mediated compartmentalization of the cell periphery, and provide new mechanistic insights into the segregation of cell-periphery proteins and their cellular functions.

scholarly journals Characterization of SCaMC-3-like/slc25a41, a novel calcium-independent mitochondrial ATP-Mg/Pi carrier

2009 ◽  
Vol 418 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Javier Traba ◽  
Jorgina Satrústegui ◽  
Araceli del Arco
Keyword(s):  
Calcium Binding ◽  
Adenine Nucleotide ◽  
Duplication Event ◽  
Intermembrane Space ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Carriers ◽  
Calcium Dependent ◽  
Mammalian Genomes ◽  
Ef Hands

The SCaMCs (small calcium-binding mitochondrial carriers) constitute a subfamily of mitochondrial carriers responsible for the ATP-Mg/Pi exchange with at least three paralogues in vertebrates. SCaMC members are proteins with two functional domains, the C-terminal transporter domain and the N-terminal domain which harbours calcium-binding EF-hands and faces the intermembrane space. In the present study, we have characterized a shortened fourth paralogue, SCaMC-3L (SCaMC-3-like; also named slc25a41), which lacks the calcium-binding N-terminal extension. SCaMC-3L orthologues are found exclusively in mammals, showing approx. 60% identity to the C-terminal half of SCaMC-3, its closest paralogue. In mammalian genomes, SCaMC-3 and SCaMC-3L genes are adjacent on the same chromosome, forming a head-to-tail tandem array, and show identical exon–intron boundaries, indicating that SCaMC-3L could have arisen from an SCaMC-3 ancestor by a partial duplication event which occurred prior to mammalian radiation. Expression and functional data suggest that, following the duplication event, SCaMC-3L has acquired more restrictive functions. Unlike the broadly expressed longer SCaMCs, mouse SCaMC-3L shows a limited expression pattern; it is preferentially expressed in testis and, at lower levels, in brain. SCaMC-3L transport activity was studied in yeast deficient in Sal1p, the calcium-dependent mitochondrial ATP-Mg/Pi carrier, co-expressing SCaMC-3L and mitochondrial-targeted luciferase, and it was found to perform ATP-Mg/Pi exchange, in a similar manner to Sal1p or other ATP-Mg/Pi carriers. However, metabolite transport through SCaMC-3L is calcium-independent, representing a novel mechanism involved in adenine nucleotide transport across the inner mitochondrial membrane, different to ADP/ATP translocases or long SCaMC paralogues.

scholarly journals Putative calcium-binding domains of theCaenorhabditis elegansBK channel are dispensable for intoxication and ethanol activation

2015 ◽  
Vol 14 (6) ◽  
pp. 454-465 ◽  
Author(s):  
S. J. Davis ◽  
L. L. Scott ◽  
G. Ordemann ◽  
A. Philpo ◽  
J. Cohn ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Binding Domains
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