VDACs: An Outlook on Biochemical Regulation and Function in Animal and Plant Systems

The voltage-dependent anion channels (VDACs) are the most abundant proteins present on the outer mitochondrial membrane. They serve a myriad of functions ranging from energy and metabolite exchange to highly debatable roles in apoptosis. Their role in molecular transport puts them on the center stage as communicators between cytoplasmic and mitochondrial signaling events. Beyond their general role as interchangeable pores, members of this family may exhibit specific functions. Even after nearly five decades of their discovery, their role in plant systems is still a new and rapidly emerging field. The information on biochemical regulation of VDACs is limited. Various interacting proteins and post-translational modifications (PTMs) modulate VDAC functions, amongst these, phosphorylation is quite noticeable. In this review, we have tried to give a glimpse of the recent advancements in the biochemical/interactional regulation of plant VDACs. We also cover a critical analysis on the importance of PTMs in the functional regulation of VDACs. Besides, the review also encompasses numerous studies which can identify VDACs as a connecting link between Ca2+ and reactive oxygen species signaling in special reference to the plant systems.

Download Full-text

Role of the Cilia Membrane in Control of Microtubule Sliding

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002683 ◽

1980 ◽

Vol 38 ◽

pp. 612-615

Author(s):

Edna S. Kaneshiro

Keyword(s):

Control Mechanism ◽

Beat Frequency ◽

Surface Membrane ◽

Ciliary Membrane ◽

Ciliary Beating ◽

Ciliary Reversal ◽

Voltage Dependent ◽

Reversal Mechanism ◽

And Function

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.

Download Full-text

In Vivo Analysis of the Major Exocytosis-sensitive Phosphoprotein in Tetrahymena

The Journal of Cell Biology ◽

10.1083/jcb.139.5.1197 ◽

1997 ◽

Vol 139 (5) ◽

pp. 1197-1207 ◽

Cited By ~ 23

Author(s):

N. Doane Chilcoat ◽

Aaron P. Turkewitz

Keyword(s):

Membrane Fusion ◽

Protein Function ◽

Potential Role ◽

Secretory Granules ◽

Rabbit Muscle ◽

Paramecium Tetraurelia ◽

Post Translational Modifications ◽

In Vivo Analysis ◽

And Function

Phosphoglucomutase (PGM) is a ubiquitous highly conserved enzyme involved in carbohydrate metabolism. A number of recently discovered PGM-like proteins in a variety of organisms have been proposed to function in processes other than metabolism. In addition, sequence analysis suggests that several of these may lack PGM enzymatic activity. The best studied PGM-like protein is parafusin, a major phosphoprotein in the ciliate Paramecium tetraurelia that undergoes rapid and massive dephosphorylation when cells undergo synchronous exocytosis of their dense-core secretory granules. Indirect genetic and biochemical evidence also supports a role in regulated exocytotic membrane fusion. To examine this matter directly, we have identified and cloned the parafusin homologue in Tetrahymena thermophila, a ciliate in which protein function can be studied in vivo. The unique T. thermophila gene, called PGM1, encodes a protein that is closely related to parafusin by sequence and by characteristic post-translational modifications. Comparison of deduced protein sequences, taking advantage of the known atomic structure of rabbit muscle PGM, suggests that both ciliate enzymes and all other PGM-like proteins have PGM activity. We evaluated the activity and function of PGM1 through gene disruption. Surprisingly, ΔPGM1 cells displayed no detectable defect in exocytosis, but showed a dramatic decrease in PGM activity. Both our results, and reinterpretation of previous data, suggest that any potential role for PGM-like proteins in regulated exocytosis is unlikely to precede membrane fusion.

Download Full-text

Knockout of Arabidopsis thaliana VEP1, Encoding a PRISE (Progesterone 5β-Reductase/Iridoid Synthase-Like Enzyme), Leads to Metabolic Changes in Response to Exogenous Methyl Vinyl Ketone (MVK)

Metabolites ◽

10.3390/metabo12010011 ◽

2021 ◽

Vol 12 (1) ◽

pp. 11

Author(s):

Jan Klein ◽

Mona Ernst ◽

Alexander Christmann ◽

Marina Tropper ◽

Tim Leykauf ◽

...

Keyword(s):

Metabolic Networks ◽

Vinyl Ketone ◽

Methyl Vinyl Ketone ◽

General Role ◽

Methyl Vinyl ◽

Knockout Mutants ◽

Number Of Genes ◽

Vein Patterning ◽

And Function

Small or specialized natural products (SNAPs) produced by plants vary greatly in structure and function, leading to selective advantages during evolution. With a limited number of genes available, a high promiscuity of the enzymes involved allows the generation of a broad range of SNAPs in complex metabolic networks. Comparative metabolic studies may help to understand why—or why not—certain SNAPs are produced in plants. Here, we used the wound-induced, vein patterning regulating VEP1 (AtStR1, At4g24220) and its paralogue gene on locus At5g58750 (AtStR2) from Arabidopsis to study this issue. The enzymes encoded by VEP1-like genes were clustered under the term PRISEs (progesterone 5β-reductase/iridoid synthase-like enzymes) as it was previously demonstrated that they are involved in cardenolide and/or iridoid biosynthesis in other plants. In order to further understand the general role of PRISEs and to detect additional more “accidental” roles we herein characterized A. thaliana steroid reductase 1 (AtStR1) and compared it to A. thaliana steroid reductase 2 (AtStR2). We used A. thaliana Col-0 wildtype plants as well as VEP1 knockout mutants and VEP1 knockout mutants overexpressing either AtStR1 or AtStR2 to investigate the effects on vein patterning and on the stress response after treatment with methyl vinyl ketone (MVK). Our results added evidence to the assumption that AtStR1 and AtStR2, as well as PRISEs in general, play specific roles in stress and defense situations and may be responsible for sudden metabolic shifts.

Download Full-text

iProteinDB: an integrative database of Drosophila post-translational modifications

10.1101/386268 ◽

2018 ◽

Cited By ~ 2

Author(s):

Yanhui Hu ◽

Richelle Sopko ◽

Verena Chung ◽

Romain A. Studer ◽

Sean D. Landry ◽

...

Keyword(s):

Protein Interactions ◽

Protein Function ◽

Large Scale ◽

Model Organisms ◽

General Strategy ◽

Post Translational Modification ◽

Post Translational Modifications ◽

Functional Sites ◽

Evolutionarily Conserved ◽

And Function

AbstractPost-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing stability, protein interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, commonly serine, threonine and tyrosine. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that many phosphorylation sites may be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites with regards to regulation and function. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from Drosophila embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for Drosophila. At iProteinDB, scientists can view the PTM landscape for any Drosophila protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related Drosophila species. Further, iProteinDB enables comparison of PTM data from Drosophila to that of orthologous proteins from other model organisms, including human, mouse, rat, Xenopus laevis, Danio rerio, and Caenorhabditis elegans.

Download Full-text

VOLTAGE-DEPENDENT HELICAL CHANNEL FORMERS: STRUCTURE AND FUNCTION

Protides of the Biological Fluids ◽

10.1016/b978-0-08-035588-7.50111-4 ◽

1987 ◽

pp. 485-488 ◽

Cited By ~ 3

Author(s):

G. JUNG ◽

R.-P. HUMMEL ◽

K.-P. VOGES ◽

C. TONIOLO ◽

G. BOHEIM

Keyword(s):

Structure And Function ◽

Helical Channel ◽

Voltage Dependent ◽

And Function

Download Full-text

Structure and Function of the Nuclear Receptor Superfamily and Current Targeted Therapies of Prostate Cancer

Cancers ◽

10.3390/cancers11121852 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1852 ◽

Cited By ~ 1

Author(s):

Baylee A. Porter ◽

Maria A. Ortiz ◽

Gennady Bratslavsky ◽

Leszek Kotula

Keyword(s):

Prostate Cancer ◽

Transcription Factors ◽

Nuclear Receptor ◽

Hormone Receptors ◽

Cell Permeability ◽

Cancer Therapies ◽

Functional Difference ◽

Nuclear Receptor Superfamily ◽

Functional Regulation ◽

And Function

The nuclear receptor superfamily comprises a large group of proteins with functions essential for cell signaling, survival, and proliferation. There are multiple distinctions between nuclear superfamily classes defined by hallmark differences in function, ligand binding, tissue specificity, and DNA binding. In this review, we utilize the initial classification system, which defines subfamilies based on structure and functional difference. The defining feature of the nuclear receptor superfamily is that these proteins function as transcription factors. The loss of transcriptional regulation or gain of functioning of these receptors is a hallmark in numerous diseases. For example, in prostate cancer, the androgen receptor is a primary target for current prostate cancer therapies. Targeted cancer therapies for nuclear hormone receptors have been more feasible to develop than others due to the ligand availability and cell permeability of hormones. To better target these receptors, it is critical to understand their structural and functional regulation. Given that late-stage cancers often develop hormone insensitivity, we will explore the strengths and pitfalls of targeting other transcription factors outside of the nuclear receptor superfamily such as the signal transducer and activator of transcription (STAT).

Download Full-text

Structure and Function of Voltage-Dependent Ion Channel Regulatory β Subunits†

Biochemistry ◽

10.1021/bi0119565 ◽

2002 ◽

Vol 41 (9) ◽

pp. 2886-2894 ◽

Cited By ~ 78

Author(s):

M. R. Hanlon ◽

B. A. Wallace

Keyword(s):

Ion Channel ◽

Structure And Function ◽

Voltage Dependent ◽

And Function

Download Full-text

Regulating NKX3.1 stability and function: Post-translational modifications and structural determinants

The Prostate ◽

10.1002/pros.23144 ◽

2016 ◽

Vol 76 (6) ◽

pp. 523-533 ◽

Cited By ~ 10

Author(s):

Achuth Padmanabhan ◽

Varsha Rao ◽

Angelo M. De Marzo ◽

Charles J. Bieberich

Keyword(s):

Structural Determinants ◽

Post Translational Modifications ◽

And Function

Download Full-text

Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms

Physiological Reviews ◽

10.1152/physrev.1996.76.3.887 ◽

1996 ◽

Vol 76 (3) ◽

pp. 887-926 ◽

Cited By ~ 193

Author(s):

H. A. Fozzard ◽

D. A. Hanck

Keyword(s):

Amino Acid ◽

Three Dimensional ◽

Point Mutations ◽

Amino Acid Sequences ◽

Na Channel ◽

Na Channels ◽

Voltage Dependent ◽

And Function ◽

Relationship Of ◽

The Relationship

Cardiac and nerve Na channels have broadly similar functional properties and amino acid sequences, but they demonstrate specific differences in gating, permeation, ionic block, modulation, and pharmacology. Resolution of three-dimensional structures of Na channels is unlikely in the near future, but a number of amino acid sequences from a variety of species and isoforms are known so that channel differences can be exploited to gain insight into the relationship of structure to function. The combination of molecular biology to create chimeras and channels with point mutations and high-resolution electrophysiological techniques to study function encourage the idea that predictions of structure from function are possible. With the goal of understanding the special properties of the cardiac Na channel, this review examines the structural (sequence) similarities between the cardiac and nerve channels and considers what is known about the relationship of structure to function for voltage-dependent Na channels in general and for the cardiac Na channels in particular.

Download Full-text

Dysregulation of chromatin organization in pediatric and adult brain tumors: oncoepigenomic contributions to tumorigenesis and cancer stem cell properties

Genome ◽

10.1139/gen-2020-0097 ◽

2020 ◽

pp. 1-11

Author(s):

Seungil Paik ◽

Francesca Maule ◽

Marco Gallo

Keyword(s):

Brain Tumors ◽

Cell Fate ◽

Three Dimensional ◽

Genetic Alterations ◽

Adult Brain ◽

Post Translational Modifications ◽

3D Genome ◽

Differentiated Cells ◽

Aberrant Dna Methylation ◽

And Function

The three-dimensional (3D) organization of the genome is a crucial enabler of cell fate, identity, and function. In this review, we will focus on the emerging role of altered 3D genome organization in the etiology of disease, with a special emphasis on brain cancers. We discuss how different genetic alterations can converge to disrupt the epigenome in childhood and adult brain tumors, by causing aberrant DNA methylation and by affecting the amounts and genomic distribution of histone post-translational modifications. We also highlight examples that illustrate how epigenomic alterations have the potential to affect 3D genome architecture in brain tumors. Finally, we will propose the concept of “epigenomic erosion” to explain the transition from stem-like cells to differentiated cells in hierarchically organized brain cancers.

Download Full-text