Volume 4 (2020)
Fine intercellular connections in development: TNTs, cytonemes, or intercellular bridges?
Olga Korenkova1,2, Anna Pepe1 and Chiara Zurzolo1
Intercellular communication is a fundamental property of multicellular organisms, necessary for their adequate responses to changing environment. Tunneling nanotubes (TNTs) represent a novel means of intercellular communication being a long cell-to-cell conduit. TNTs are actively formed under a broad range of stresses and are also proposed to exist under physiological conditions. Development is a physiological condition of particular interest, as it requires fine coordination. Here we discuss whether protrusions shown to exist during embryonic development of different species could be TNTs or if they represent other types of cell structure, like cytonemes or intercellular bridges, that are suggested to play an important role in development.
Kynurenine: an oncometabolite in colon cancer
Niranjan Venkateswaran1 and Maralice Conacci-Sorrell1,2,3
TRYPTOPHAN IS PREFERENTIALLY CONVERTED INTO KYNURENINE IN COLON CANCER Tryptophan can be utilized in three ways intracellularly: it can be incorporated into newly synthesized proteins, it can be processed by
Exocytotic fusion pore under stress
Helena Haque Chowdhury1,2 and Robert Zorec1,2
Exocytosis is a universal process of eukaryotic cells, consisting of fusion between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a channel through which vesicle cargo exits into the extracellular space. In 1986, Rand and Parsegian proposed several stages to explain the nature of membrane fusion. Following stimulation, it starts with focused stress destabilization of membranes in contact, followed by the coalescence of two membrane surfaces. In the next fraction of a millisecond, restabilization of fused membranes is considered to occur to maintain the cell's integrity. This view predicted that once a fusion pore is formed, it must widen abruptly, irreversibly and fully, whereby the vesicle membrane completely integrates with and collapses into the plasma membrane (full fusion exocytosis). However, recent experimental evidence has revealed that once the fusion pore opens, it may also reversibly close (transient or kiss-and-run exocytosis). Here, we present a historical perspective on understanding the mechanisms that initiate (...)
Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy
Daniel Baumann1,2 and Rienk Offringa1,2
– [table id=351/] IDENTIFYING SUITABLE CYTOSTATIC DRUGS FOR COMBINATORIAL IMMUNOTHERAPY The main dilemma in finding combinations of cytostatic and immunostimulatory drugs that act synergistically is as follows. On the one
Hyaluronan goes to great length
Vera Gorbunova1, Masaki Takasugi1 and Andrei Seluanov1
The naked mole rat is the longest-lived rodent with the maximum lifespan of over 35 years. Naked mole rats are protected from a wide range of age-related diseases including cancer,
PRMT5 function and targeting in cancer
Hyungsoo Kim1 and Ze’ev A. Ronai1
Protein methyl transferases play critical roles in numerous regulatory pathways that underlie cancer development, progression and therapy-response. Here we discuss the function of PRMT5, a member of the nine-member PRMT family, in controlling oncogenic processes including tumor intrinsic, as well as extrinsic microenvironmental signaling pathways. We discuss PRMT5 effect on histone methylation and methylation of regulatory proteins including those involved in RNA splicing, cell cycle, cell death and metabolic signaling. In all, we highlight the importance of PRMT5 regulation and function in cancer, which provide the foundation for therapeutic modalities targeting PRMT5.
Regulation of immune checkpoint blockade efficacy in breast cancer by FIP200: A canonical-autophagy-independent function
Syn Kok Yeo1 and Jun-Lin Guan1
DISSECTING THE ROLE OF AUTOPHAGY AND AUTOPHAGY-INDEPENDENT FUNCTIONS OF FIP200 IN BREAST CANCER Although initial studies of autophagy genes in cancer implicated a tumor suppressive role, it has become apparent
Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma
James J. Hsieh1 and Emily H. Cheng2,3,4
INTRODUCTION On average a human adult body encompasses fifty trillion cells (~5×1013) with a daily turnover of hundred billion cells (~1011) within which each contains two copies of ~three billion
High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer’s disease
Maria Calvo-Rodriguez1 and Brian J. Bacskai1
MITOCHONDRIAL CALCIUM OVERLOAD AFTER PLAQUE DEPOSITION Ca2+ is essential for the normal function of mitochondrial activity, and therefore Ca2+ levels are tightly regulated in mitochondria. However, excessive levels of Ca2+
The role of lipids in autophagy and its implication in neurodegeneration
Sergio Hernandez-Diaz1,2 and Sandra-Fausia Soukup1,2
Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.
Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment
Alejandra Gomez-Cadena1,2,3, Alfonso Barreto3, Susana Fiorentino3 and Camilla Jandus1,2
INTRODUCTION Over the past decade, immunotherapy has become a promising approach to treat cancer and is now being combined with standard chemotherapy and immune response activators to improve the outcome
Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond
Shin-Haw Lee1,2, Sina Hadipour-Lakmehsari1,2 and Anthony O. Gramolini1,2
DISCOVERY OF REEP5 Cardiac membrane proteins play an important role in regulating normal beat-to-beat function of the heart given their importance in coordinating spontaneous contractions of cardiomyocytes in the heart.
Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases
Gina Picchiarelli1 and Luc Dupuis1
A number of neuromuscular and muscular diseases, including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and several myopathies, are associated to mutations in related RNA-binding proteins (RBPs), including TDP-43, FUS, MATR3 or hnRNPA1/B2. These proteins harbor similar modular primary sequence with RNA binding motifs and low complexity domains, that enables them to phase separate and create liquid microdomains. These RBPs have been shown to critically regulate multiple events of RNA lifecycle, including transcriptional events, splicing and RNA trafficking and sequestration. Here, we review the roles of these disease-related RBPs in muscle and motor neurons, and how their dysfunction in these cell types might contribute to disease.
Biomechanical stress regulates mammalian tooth replacement
Xiaoshan Wu1,2 and Songlin Wang1,3
The DT eruption released a biomechanical stress of about 3-20 kPa inside the mandible. By culturing the mandible slice in vitro, the SDL of the PT immediately transitioned into the
Biomechanical stress provides a second hit in the establishment of BMP/TGFβ-related vascular disorders
Christian Hiepen1, Jerome Jatzlau1 and Petra Knaus1
BMPR2 MUTATIONS PRIME FOR PAH BUT REQUIRE A SECOND HIT While BMPR2 mutations appear as one of the main genetic drivers for HPAH, low BMPR2 expression is also found in
Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma
James J. Hsieh1 and Emily H. Cheng2,3,4
INTRODUCTION On average a human adult body encompasses fifty trillion cells (~5×1013) with a daily turnover of hundred billion cells (~1011) within which each contains two copies of ~three billion
HIF1α or mitophagy: which drives cardiomyocyte differentiation?
Beatriz Villarejo-Zori1,#, Juan Ignacio Jiménez-Loygorri1,# and Patricia Boya1
Cardiomyocytes (CMs) are the main cellular component of the heart's atria and ventricles, and their contractile capacity is the engine that drives blood flow throughout the body. The differentiation of
Copper – a novel stimulator of autophagy
Hans Zischka1,2 and Guido Kroemer3-7
In biomedicine, the transition metal copper has a Janus-faced dual role, as an essential but static cofactor of vital enzymes but also as a highly detrimental poison, if in excess.
Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses
Didier Raoult1, Alimuddin Zumla2,3, Franco Locatelli4, Giuseppe Ippolito5 and Guido Kroemer6-10,*
INTRODUCTION Infections have been limiting quality of life and longevity throughout human history. Endemic infections have been associated to a significant number of avoidable deaths and a significant increase of
ACBP is an appetite stimulator across phylogenetic barriers
Frank Madeo1,2, Nektarios Tavernarakis3,4, José M. Bravo-San Pedro5-7,# and Guido Kroemer5-10,#
Human civilization is unique with respect to the organization of our natural environment, allowing constant supply of nutrients to most individuals in developed countries, contrasting with the natural fluctuation in