scholarly journals Differential Effects of Prenylation and S-Acylation on Type I and II ROPS Membrane Interaction and Function

2010 ◽  
Vol 155 (2) ◽  
pp. 706-720 ◽  
Author(s):  
Nadav Sorek ◽  
Orit Gutman ◽  
Einat Bar ◽  
Mohamad Abu-Abied ◽  
Xuehui Feng ◽  
...  
Keyword(s):  
Type I ◽  
Membrane Interaction ◽  
Differential Effects ◽  
And Function

Type I Interferons promote maintenance and function of follicular T helper cells in vitro

2019 ◽  
Author(s):  
S Ehrlich ◽  
K Wild ◽  
M Smits ◽  
K Zoldan ◽  
M Hofmann ◽  
...  
Keyword(s):  
T Helper Cells ◽  
Type I Interferons ◽  
Type I ◽  
T Helper ◽  
Helper Cells ◽  
Follicular T Helper Cells ◽  
And Function

Collagen-the Ultrastructural Element of the Bone Matrix

2018 ◽  
Vol 69 (7) ◽  
pp. 1706-1709
Author(s):  
Nicoleta Dumitru ◽  
Andra Cocolos ◽  
Andra Caragheorgheopol ◽  
Constantin Dumitrache ◽  
Ovidiu Gabriel Bratu ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Bone Microarchitecture ◽  
Complex Structure ◽  
Bone Matrix ◽  
Organic Matrix ◽  
Bone Diseases ◽  
Bone Collagen ◽  
Type I ◽  
New Therapeutic Approaches ◽  
And Function

There is an increased interest and more studies highlight the fact that bone strength depends not only on bone tissue quantity, but also on its quality, which is characterized by the geometry and shape of bones, trabecular bone microarchitecture, mineral content, organic matrix and bone turnover. Fibrillar type I collagen is the major organic component of bone matrix, providing form and a stable template for mineralization. The biomedical importance of collagen as a biomaterial for medical and cosmetic purposes and the improvement of the molecular, cellular biology and analytical technologies, led to increasing interest in establishing the structure of this protein and in setting of the relationships between sequence, structure, and function. Bone collagen crosslinking chemistry and its molecular packing structure are considered to be distinct features. This unique post-translational modifications provide to the fibrillar collagen matrices properties such as tensile strength and viscoelasticity. Understanding the complex structure of bone type I collagen as well as the dynamic nature of bone tissues will help to manage new therapeutic approaches to bone diseases.

scholarly journals The Drosophila engrailed and invected Genes: Partners in Regulation, Expression and Function

Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 893-906 ◽  
Author(s):  
Elizabeth Gustavson ◽  
Andrew S Goldsborough ◽  
Zehra Ali ◽  
Thomas B Kornberg
Keyword(s):  
Expression Pattern ◽  
Cultured Cells ◽  
Regulatory Region ◽  
Embryonic Lethality ◽  
Wild Type ◽  
Terminal Portion ◽  
Coding Sequence ◽  
Differential Effects ◽  
And Function ◽  
Redundant Functions

Abstract We isolated and characterized numerous engrailed and invected alleles. Among the deficiencies we isolated, a mutant lacking invected sequences was viable and phenotypically normal, a mutant lacking engrailed was an embryo lethal and had slight segmentation defects, and a mutant lacking both engrailed and invected was most severely affected. In seven engrailed alleles, mutations caused translation to terminate prematurely in the central or C-terminal portion of the coding sequence, resulting in embryonic lethality and segmentation defects. Both engrailed and invected expression declined prematurely in these mutant embryos. In wild-type embryos, engrailed and invected are juxtaposed and are expressed in essentially identical patterns. A breakpoint mutant that separates the mgrailed and invected transcription units parceled different aspects of the expression pattern to engrailed or invected. We also found that both genes cause similar defects when expressed ectopically and that the protein products of both genes act to repress transcription in cultured cells. We propose that the varied phenotypes of the engrailed alleles can be explained by the differential effects these mutants have on the combination of engrailed and invected activities, that engrailed and invected share a regulatory region, and that they encode redundant functions.

scholarly journals Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B

2021 ◽  
Vol 22 (5) ◽  
pp. 2501
Author(s):  
Sonja Hinz ◽  
Dominik Jung ◽  
Dorota Hauert ◽  
Hagen S. Bachmann
Keyword(s):  
Protein Function ◽  
Tumor Development ◽  
Cysteine Residue ◽  
Type I ◽  
Pharmacological Characterization ◽  
Anti Cancer ◽  
And Function ◽  
Caax Motif ◽  
Important Drug

Geranylgeranyltransferase type-I (GGTase-I) represents an important drug target since it contributes to the function of many proteins that are involved in tumor development and metastasis. This led to the development of GGTase-I inhibitors as anti-cancer drugs blocking the protein function and membrane association of e.g., Rap subfamilies that are involved in cell differentiation and cell growth. In the present study, we developed a new NanoBiT assay to monitor the interaction of human GGTase-I and its substrate Rap1B. Different Rap1B prenylation-deficient mutants (C181G, C181S, and ΔCQLL) were designed and investigated for their interaction with GGTase-I. While the Rap1B mutants C181G and C181S still exhibited interaction with human GGTase-I, mutant ΔCQLL, lacking the entire CAAX motif (defined by a cysteine residue, two aliphatic residues, and the C-terminal residue), showed reduced interaction. Moreover, a specific, peptidomimetic and competitive CAAX inhibitor was able to block the interaction of Rap1B with GGTase-I. Furthermore, activation of both Gαs-coupled human adenosine receptors, A2A (A2AAR) and A2B (A2BAR), increased the interaction between GGTase-I and Rap1B, probably representing a way to modulate prenylation and function of Rap1B. Thus, A2AAR and A2BAR antagonists might be promising candidates for therapeutic intervention for different types of cancer that overexpress Rap1B. Finally, the NanoBiT assay provides a tool to investigate the pharmacology of GGTase-I inhibitors.

scholarly journals Actin-membrane interaction in fibroblasts: what proteins are involved in this association?

1984 ◽  
Vol 99 (1) ◽  
pp. 95s-103s ◽  
Author(s):  
P Mangeat ◽  
K Burridge
Keyword(s):  
Plasma Membrane ◽  
Actin Filaments ◽  
Stress Fiber ◽  
Membrane Interaction ◽  
Microfilament Bundles ◽  
The Family ◽  
Form Part ◽  
Membrane Attachment ◽  
A Chain ◽  
And Function

In this review we discuss some of the proteins for which a role in linking actin to the fibroblast plasma membrane has been suggested. We focus on the family of proteins related to erythrocyte spectrin, proteins that have generally been viewed as having an organization and a function in actin-membrane attachment similar to those of erythrocyte spectrin. Experiments in which we precipitated the nonerythrocyte spectrin within living fibroblasts have led us to question this supposed similarity of organization and function of the nonerythrocyte and erythrocyte spectrins. Intracellular precipitation of fibroblast spectrin does not affect the integrity of the major actin-containing structures, the stress fiber microfilament bundles. Unexpectedly, however, we found that the precipitation of spectrin results in a condensation and altered distribution of the vimentin class of intermediate filaments in most cells examined. Although fibroblast spectrin may have a role in the attachment of some of the cortical, submembranous actin, it is surprising how little the intracellular immunoprecipitation of the spectrin affects the cells. Several proteins have been found concentrated at the ends of stress fibers, where the actin filaments terminate at focal contacts. Two of these proteins, alpha-actinin and fimbrin, have properties that suggest that they are not involved in the attachment of the ends of the bundles to the membrane but are more probably involved in the organization and cross-linking of the filaments within the bundles. On the other hand, vinculin and talin are two proteins that interact with each other and may form part of a chain of attachments between the ends of the microfilament bundles and the focal contact membrane. Their role in this attachment, however, has not been established and further work is needed to examine their interaction with actin and to identify any other components with which they may interact, particularly in the plasma membrane.

Differential effects of the ApoE4 genotype on brain structure and function

NeuroImage ◽  
2014 ◽  
Vol 89 ◽  
pp. 81-91 ◽  
Author(s):  
Silke Matura ◽  
David Prvulovic ◽  
Alina Jurcoane ◽  
Daniel Hartmann ◽  
Julia Miller ◽  
...  
Keyword(s):  
Brain Structure ◽  
Structure And Function ◽  
Differential Effects ◽  
Brain Structure And Function ◽  
And Function

scholarly journals Transcriptional Changes in Regulatory T Cells From Patients With Autoimmune Polyendocrine Syndrome Type 1 Suggest Functional Impairment of Lipid Metabolism and Gut Homing

2021 ◽  
Vol 12 ◽  
Author(s):  
Amund Holte Berger ◽  
Eirik Bratland ◽  
Thea Sjøgren ◽  
Marte Heimli ◽  
Torgeir Tyssedal ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Type I ◽  
Syndrome Type ◽  
Functional Studies ◽  
Autoimmune Polyendocrine Syndrome ◽  
Organ Specific ◽  
Hla Dqa1 ◽  
And Function ◽  
The Impact

Autoimmune polyendocrine syndrome type I (APS-1) is a monogenic model disorder of organ-specific autoimmunity caused by mutations in the Autoimmune regulator (AIRE) gene. AIRE facilitates the expression of organ-specific transcripts in the thymus, which is essential for efficient removal of dangerous self-reacting T cells and for inducing regulatory T cells (Tregs). Although reduced numbers and function of Tregs have been reported in APS-I patients, the impact of AIRE deficiency on gene expression in these cells is unknown. Here, we report for the first time on global transcriptional patterns of isolated Tregs from APS-1 patients compared to healthy subjects. Overall, we found few differences between the groups, although deviant expression was observed for the genes TMEM39B, SKIDA1, TLN2, GPR15, FASN, BCAR1, HLA-DQA1, HLA-DQB1, HLA-DRA, GPSM3 and AKR1C3. Of significant interest, the consistent downregulation of GPR15 may indicate failure of Treg gut homing which could be of relevance for the gastrointestinal manifestations commonly seen in APS-1. Upregulated FASN expression in APS-1 Tregs points to increased metabolic activity suggesting a putative link to faulty Treg function. Functional studies are needed to determine the significance of these findings for the immunopathogenesis of APS-1 and for Treg immunobiology in general.

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