Role of ERLINs in the Control of Cell Fate through Lipid Rafts

ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP3) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the “interchange” between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases.

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From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

Polysaccharides ◽

10.3390/polysaccharides2020021 ◽

2021 ◽

Vol 2 (2) ◽

pp. 311-338

Author(s):

Giulia Della Rosa ◽

Clarissa Ruggeri ◽

Alessandra Aloisi

Keyword(s):

State Of The Art ◽

Cell Communication ◽

Pathological Conditions ◽

New Findings ◽

Cell Type Specific ◽

New Perspective ◽

And Function ◽

And Personalized Medicine ◽

Innate Ability

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

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The Recent Understanding of the Neurotrophin's Role in Skeletal Muscle Adaptation

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/201696 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 51

Author(s):

Kunihiro Sakuma ◽

Akihiko Yamaguchi

Keyword(s):

Skeletal Muscle ◽

Neuromuscular Disorders ◽

Muscle Fibers ◽

Brain Disorders ◽

Muscle Adaptation ◽

Bdnf Mrna ◽

Pathological Conditions ◽

Development And Differentiation ◽

And Function

This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise) produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression). In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease.

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The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

AJP Renal Physiology ◽

10.1152/ajprenal.00059.2021 ◽

2021 ◽

Author(s):

Diana Hamdan ◽

Lisa A. Robinson

Keyword(s):

Therapeutic Potential ◽

Kidney Diseases ◽

Transmembrane Protein ◽

Soluble Form ◽

Protective Effects ◽

Chronic Kidney Diseases ◽

The Family ◽

Soluble Species ◽

And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

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PIN-FORMED 1 regulates cell fate at the periphery of the shoot apical meristem

Development ◽

10.1242/dev.127.23.5157 ◽

2000 ◽

Vol 127 (23) ◽

pp. 5157-5165 ◽

Cited By ~ 13

Author(s):

T. Vernoux ◽

J. Kronenberger ◽

O. Grandjean ◽

P. Laufs ◽

J. Traas

Keyword(s):

Cell Fate ◽

Apical Meristem ◽

Transmembrane Protein ◽

Loss Of Function ◽

Hybrid Identity ◽

Hormone Transport ◽

Early Markers ◽

Ideal Tool ◽

And Function

The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis.

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MYOSTATIN - A MODERN UNDERSTANDING OF THE PHYSIOLOGICAL ROLE AND SIGNIFICANCE IN THE DEVELOPMENT OF AGE-ASSOCIATED DISEASES

Успехи геронтологии ◽

10.34922/ae.2021.34.5.005 ◽

2021 ◽

pp. 701-706

Author(s):

А.А. Газданова ◽

В.Г. Кукес ◽

О.К. Парфенова ◽

Н.Г. Сидоров ◽

А.В. Перков ◽

...

Keyword(s):

Muscle Growth ◽

Physiological Role ◽

Review Article ◽

Negative Regulator ◽

Transforming Growth Factors ◽

Endogenous Factors ◽

Pathological Conditions ◽

Physiological Properties ◽

The Family

Миостатин - белок, принадлежащий к классу миокинов, семейству трансформирующих факторов роста β (TGF-β). В обзорной статье, анализирующей данные литературы, показана ключевая роль миостатина в развитии старческой саркопении и кахексии при различных патологических состояниях, таких как рак, ХСН, ХБП, ХОБЛ и др. В статье рассматривается структура миостатина, подробная схема синтеза и его активации, механизм действия как негативного регулятора роста и дифференцировки мышц при этих патологических состояниях. Выделены основные физиологические свойства и клиническое значение. Рассмотрены экзогенные и эндогенные факторы, регулирующие экспрессию миостатина, и возможные механизмы их действия. Myostatin is a protein belonging to the myokine class, the family of transforming growth factors β (TGF-β). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions. The main physiological properties and clinical significance are highlighted. Exogenous and endogenous factors regulating myostatin expression and possible mechanisms of their action are considered.

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Relevance of Fatty Acids to Sperm Maturation and Quality

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7038124 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 6

Author(s):

Giulia Collodel ◽

Cesare Castellini ◽

Jetty Chung-Yung Lee ◽

Cinzia Signorini

Keyword(s):

Biological Sciences ◽

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Profile ◽

Human Sperm ◽

Dietary Fatty Acids ◽

Pathological Conditions ◽

Sperm Membrane ◽

And Function

Almost 50% of infertility cases are associated with human male infertility. The sperm membrane is a key structure influencing sperm morphology and function in normal and pathological conditions. The fatty acid profile determines the performance not only of sperm motility but also of acrosomal reaction and sperm-oocyte fusion. This review presents available knowledge on the role of fatty acid composition in human sperm and spermatogenesis and discusses the influence of dietary fatty acids on the sperm fatty acid profile. Recent studies in biological sciences and clinical researches in this field are also reported. The topic object of this review has potential application in medicine by identifying potential causes of infertility.

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The Role of Family Hope Program Actor in Empowering Poor Society (Case Study of Bone Regency) Indonesia

Journal of Public Administration and Governance ◽

10.5296/jpag.v9i2.14875 ◽

2019 ◽

Vol 9 (2) ◽

pp. 359

Author(s):

Misnawati Misnawati ◽

Hasbi ◽

Abd Rasyid J ◽

Yusriadi Yusriadi ◽

Saidna Zulfiqar Bin-Tahir

Keyword(s):

Data Collection ◽

Poverty Alleviation ◽

Case Study Research ◽

Data Presentation ◽

Analysis Techniques ◽

The Family ◽

Collection Data ◽

And Function

The Family Hope Program (PKH) is one of government policy programs in poverty alleviation by involving the main actor who called PPKH. This study aimed to describe the task and function of PPKH in empowering the sick society in Bone Regency. Qualitative approach used with case study research. Data collection techniques used was interviews, observation, and documentation. The instrument in this study was the researcher himself as a human instrument, while the informants selected by a purposive method. Data analysis techniques used an interactive model includes data collection, data reduction, data presentation, verification, and conclusion. The results of the study showed that PPKH has carried out their roles well as representatives and technicians but have not been optimal in their roles as facilitators and educators.

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Structural Insight into the Mechanism of N-Linked Glycosylation by Oligosaccharyltransferase

Biomolecules ◽

10.3390/biom10040624 ◽

2020 ◽

Vol 10 (4) ◽

pp. 624 ◽

Cited By ~ 2

Author(s):

Smita Mohanty ◽

Bharat P Chaudhary ◽

David Zoetewey

Keyword(s):

Endoplasmic Reticulum ◽

Protein Modification ◽

Cell Communication ◽

Reticulum Cell ◽

Enzyme Complex ◽

Single Polypeptide Chain ◽

Domains Of Life ◽

And Function ◽

Insight Into

Asparagine-linked glycosylation, also known as N-linked glycosylation is an essential and highly conserved post-translational protein modification that occurs in all three domains of life. This modification is essential for specific molecular recognition, protein folding, sorting in the endoplasmic reticulum, cell–cell communication, and stability. Defects in N-linked glycosylation results in a class of inherited diseases known as congenital disorders of glycosylation (CDG). N-linked glycosylation occurs in the endoplasmic reticulum (ER) lumen by a membrane associated enzyme complex called the oligosaccharyltransferase (OST). In the central step of this reaction, an oligosaccharide group is transferred from a lipid-linked dolichol pyrophosphate donor to the acceptor substrate, the side chain of a specific asparagine residue of a newly synthesized protein. The prokaryotic OST enzyme consists of a single polypeptide chain, also known as single subunit OST or ssOST. In contrast, the eukaryotic OST is a complex of multiple non-identical subunits. In this review, we will discuss the biochemical and structural characterization of the prokaryotic, yeast, and mammalian OST enzymes. This review explains the most recent high-resolution structures of OST determined thus far and the mechanistic implication of N-linked glycosylation throughout all domains of life. It has been shown that the ssOST enzyme, AglB protein of the archaeon Archaeoglobus fulgidus, and the PglB protein of the bacterium Campylobactor lari are structurally and functionally similar to the catalytic Stt3 subunit of the eukaryotic OST enzyme complex. Yeast OST enzyme complex contains a single Stt3 subunit, whereas the human OST complex is formed with either STT3A or STT3B, two paralogues of Stt3. Both human OST complexes, OST-A (with STT3A) and OST-B (containing STT3B), are involved in the N-linked glycosylation of proteins in the ER. The cryo-EM structures of both human OST-A and OST-B complexes were reported recently. An acceptor peptide and a donor substrate (dolichylphosphate) were observed to be bound to the OST-B complex whereas only dolichylphosphate was bound to the OST-A complex suggesting disparate affinities of two OST complexes for the acceptor substrates. However, we still lack an understanding of the independent role of each eukaryotic OST subunit in N-linked glycosylation or in the stabilization of the enzyme complex. Discerning the role of each subunit through structure and function studies will potentially reveal the mechanistic details of N-linked glycosylation in higher organisms. Thus, getting an insight into the requirement of multiple non-identical subunits in the N-linked glycosylation process in eukaryotes poses an important future goal.

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CREB regulates the expression of Type 1 Inositol 1,4,5-trisphosphate receptors

Journal of Cell Science ◽

10.1242/jcs.258875 ◽

2021 ◽

Author(s):

Vikas Arige ◽

Lara E. Terry ◽

Sundeep Malik ◽

Taylor R. Knebel ◽

Larry E. Wagner ◽

...

Keyword(s):

Long Term Effects ◽

Ip3 Receptors ◽

Chronic Stimulation ◽

Interacting Protein ◽

Post Translational Modifications ◽

Over Expression ◽

Pathological Conditions ◽

Inositol 1,4,5 Trisphosphate

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) play a central role in regulating intracellular calcium signals in response to a variety of internal/external cues. Dysregulation of IP3R signaling is the underlying cause for numerous pathological conditions. It is well established that the activities of IP3Rs are governed by several post-translational modifications including phosphorylation by protein kinase A (PKA). However, the long-term effects of PKA activation on expression of IP3R sub-types, remains largely unexplored. In this report, we investigate the effects of more chronic stimulation and tonic activity of PKA on the expression of IP3R sub-types. We demonstrate that the expression of IP3R1 is augmented upon prolonged activation of PKA or upon ectopic over-expression of CREB without altering IP3R2 and IP3R3 abundance. Conversely, inhibition of PKA or blocking CREB diminished IP3R1 expression. We also demonstrate that agonist-induced Ca2+-release mediated by IP3R1 is significantly attenuated upon blocking CREB. Moreover, CREB by regulating the expression of KRAS-induced actin-interacting protein (KRAP) ensures proper localization and licensing of IP3R1. Overall, we report a crucial role for CREB in governing both the expression and proper localization of IP3R1.

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DISORIENTASI PENDIDIKAN MADRASAH DI INDONESIA

POTENSIA Jurnal Kependidikan Islam ◽

10.24014/potensia.v3i1.3470 ◽

2017 ◽

Vol 3 (1) ◽

pp. 61

Author(s):

Hasan Basri

Keyword(s):

School Culture ◽

Secular Education ◽

The Family ◽

The Status ◽

The Will ◽

And Function ◽

Changing Schools ◽

Further Development

Madrasah in the Middle East has known eight or nine centuries before madrasah in Indonesia, which emerged as a reaction to the reform movement as well as a response to the policy of Dutch colonizers secular education. Madrasah got a decent place in Indonesia after rising SKB 3 minister (Minister of Interior, Minister of Education and Culture, and the Minister of Religious Affairs) in 1975, where madrasas equated with other schools in terms of the status of the diploma, graduates continuing education opportunities and changing schools. In a further development, the school as disoriented. It is caused by two things: first, a paradigm shift towards sekularistik. Education implementation has marred even be interpreted as a partial instead of a holistic paradigm as desired by Islam. Supposedly, the madrasa education as a whole should make Islam as a principle in the determination of educational objectives, the formulation of the curriculum and standard of value of science and the learning process, including determining the qualifications of teachers and school culture that will be developed in the madrasas. Second, the functional institutional weakness as a result of shifting the orientation and function of the family and their influence and societal demands materialistic-hedonistic.The weakness seen in a mess madrasa curriculum, not optimal role of teachers as well as school culture that is not in line with the will of Islam.

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