Reviews
Roles of phosphatidyl inositol 3 kinase gamma (PI3Kγ) in respiratory diseases
Valentina Sala1, Angela Della Sala1, Alessandra Ghigo1,2,# and Emilio Hirsch1,2,#
Phosphatidyl inositol 3 kinase gamma (PI3Kγ) is expressed in all the cell types that are involved in airway inflammation and disease, including not only leukocytes, but also structural cells, where it is expressed at very low levels under physiological conditions, while is significantly upregulated after stress. In the airways, PI3Kγ behaves as a trigger or a controller, depending on the pathological context. In this review, the contribution of PI3Kγ in a plethora of respiratory diseases, spanning from acute lung injury, pulmonary fibrosis, asthma, cystic fibrosis and response to both bacterial and viral pathogens, will be commented.
Endocytosis in the adaptation to cellular stress
Tania López-Hernández1, Volker Haucke1,2 and Tanja Maritzen1
Cellular life is challenged by a multitude of stress conditions, triggered for example by alterations in osmolarity, oxygen or nutrient supply. Hence, cells have developed sophisticated stress responses to cope with these challenges. Some of these stress programs such as the heat shock response are understood in great detail, while other aspects remain largely elusive including potential stress-dependent adaptations of the plasma membrane proteome. The plasma membrane is not only the first point of encounter for many types of environmental stress, but given the diversity of receptor proteins and their associated molecules also represents the site at which many cellular signal cascades originate. Since these signaling pathways affect virtually all aspects of cellular life, changes in the plasma membrane proteome appear ideally suited to contribute to the cellular adaptation to stress. The most rapid means to alter the cell surface proteome in response to stress is by alterations in endocytosis. Changes in the overall endocytic flux or in the endocytic (...)
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 (...)
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.
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