scholarly journals The Glyco-enzyme adaptor GOLPH3 Links Intra-Golgi Transport Dynamics to Glycosylation Patterns and Cell Proliferation

2019 ◽  
Author(s):  
Riccardo Rizzo ◽  
Domenico Russo ◽  
Kazuo Kurokawa ◽  
Pranoy Sahu ◽  
Bernadette Lombardi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Specific Growth ◽  
Transport Mechanisms ◽  
Biological Functions ◽  
Lysosomal Degradation ◽  
Transport Dynamics ◽  
Cell Functions ◽  
Golgi Transport ◽  
Organizing Principles

AbstractGlycans are ubiquitous sugar polymers with major biological functions that are assembled by glyco-enzymes onto cargo molecules during their transport through the Golgi complex. How the Golgi determines glycan assembly is poorly understood. By relying on the Golgi cisternal maturation model and using the glyco-enzyme adaptor and oncoprotein GOLPH3 as a molecular tool, we define the first example of how the Golgi controls glycosylation and associated cell functions. GOLPH3, acting as a component of the cisternal maturation mechanism, selectively binds and recycles a subset of glyco-enzymes of the glycosphingolipid synthetic pathway, hinders their escape to the lysosomes and hence increases their levels through a novel lysosomal degradation-regulated mechanism. This enhances the production of specific growth-inducing glycosphingolipids and reprograms the glycosphingolipid pathway to potentiate mitogenic signaling and cell proliferation. These findings unravel unforeseen organizing principles of Golgi-dependent glycosylation and delineate a paradigm for glycan assembly by the Golgi transport mechanisms. Moreover, they indicate a new role of cisternal maturation as a regulator of glycosylation, and outline a novel mechanism of action for GOLPH3-induced proliferation.

scholarly journals Targeting lysosomes in human disease: from basic research to clinical applications

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mengdie Cao ◽  
Xiangyuan Luo ◽  
Kongming Wu ◽  
Xingxing He
Keyword(s):  
Cell Proliferation ◽  
Human Disease ◽  
Basic Research ◽  
Clinical Findings ◽  
Clinical Applications ◽  
Biological Functions ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Lysosomal Acidification

AbstractIn recent years, accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis. Lysosomal changes and dysfunction have been correlated with the development of numerous diseases. In this review, we interpreted the key biological functions of lysosomes in four areas: cellular metabolism, cell proliferation and differentiation, immunity, and cell death. More importantly, we actively sought to determine the characteristic changes and dysfunction of lysosomes in cells affected by these diseases, the causes of these changes and dysfunction, and their significance to the development and treatment of human disease. Furthermore, we outlined currently available targeting strategies: (1) targeting lysosomal acidification; (2) targeting lysosomal cathepsins; (3) targeting lysosomal membrane permeability and integrity; (4) targeting lysosomal calcium signaling; (5) targeting mTOR signaling; and (6) emerging potential targeting strategies. Moreover, we systematically summarized the corresponding drugs and their application in clinical trials. By integrating basic research with clinical findings, we discussed the current opportunities and challenges of targeting lysosomes in human disease.

scholarly journals A Cahn–Hilliard–Darcy model for tumour growth with chemotaxis and active transport

2016 ◽  
Vol 26 (06) ◽  
pp. 1095-1148 ◽  
Author(s):  
Harald Garcke ◽  
Kei Fong Lam ◽  
Emanuel Sitka ◽  
Vanessa Styles
Keyword(s):  
Active Transport ◽  
Tumour Growth ◽  
Specific Growth ◽  
Matched Asymptotic Expansion ◽  
Transport Mechanisms ◽  
Darcy Model ◽  
Nutrient Density ◽  
Nutrient Diffusion ◽  
Transport Term

Using basic thermodynamic principles we derive a Cahn–Hilliard–Darcy model for tumour growth including nutrient diffusion, chemotaxis, active transport, adhesion, apoptosis and proliferation. In contrast to earlier works, the model is based on a volume-averaged velocity and in particular includes active transport mechanisms which ensure thermodynamic consistency. We perform a formally matched asymptotic expansion and develop several sharp interface models. Some of them are classical and some are new which for example include a jump in the nutrient density at the interface. A linear stability analysis for a growing nucleus is performed and in particular the role of the new active transport term is analysed. Numerical computations are performed to study the influence of the active transport term for specific growth scenarios.

scholarly journals Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer

2016 ◽  
Vol 44 (5) ◽  
pp. 1347-1354 ◽  
Author(s):  
Elena Rainero
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Secreted Proteins ◽  
Oncogenic Transformation ◽  
Intracellular Degradation ◽  
Cell Functions ◽  
Ecm Degradation

The extracellular matrix (ECM) is a network of secreted proteins that, beyond providing support for tissues and organs, is involved in the regulation of a variety of cell functions, including cell proliferation, polarity, migration and oncogenic transformation. ECM homeostasis is maintained through a tightly controlled balance between synthesis, deposition and degradation. While the role of metalloproteases in ECM degradation is widely recognised, the contribution of ECM internalisation and intracellular degradation to ECM maintenance has been mostly overlooked. In this review, I will summarise what is known about the molecular mechanisms mediating ECM endocytosis and how this process impacts on diseases, such as fibrosis and cancer.

scholarly journals Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Yang ◽  
Chaoju Gong ◽  
Qinjian Ke ◽  
Zejun Fang ◽  
Xiaowen Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Regulatory Mechanisms ◽  
Biological Functions ◽  
Multiple Cancer ◽  
Aberrant Expression ◽  
Cancer Management ◽  
Cancer Types ◽  
Proliferation And Invasion

Histone deacetylase 5 (HDAC5) is a class II HDAC. Aberrant expression of HDAC5 has been observed in multiple cancer types, and its functions in cell proliferation and invasion, the immune response, and maintenance of stemness have been widely studied. HDAC5 is considered as a reliable therapeutic target for anticancer drugs. In light of recent findings regarding the role of epigenetic reprogramming in tumorigenesis, in this review, we provide an overview of the expression, biological functions, regulatory mechanisms, and clinical significance of HDAC5 in cancer.

scholarly journals Mitochondrial Disorders Therapy: The Utility of Melatonin

2010 ◽  
Vol 3 (1) ◽  
pp. 53-65
Author(s):  
Luis C. Lopez ◽  
Dario Acuna-Castroviejo ◽  
Alberto del Pino ◽  
Miguel Tejada ◽  
Germaine Escames
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Action Spectrum ◽  
Cell Physiology ◽  
Stem Cell Proliferation ◽  
Cell Functions ◽  
Mtdna Mutations ◽  
Mitochondrial Homeostasis

Mitochondria play a central role in the cell physiology. It is now recognized that, besides their classic function of energy metabolism, mitochondria are enrolled in multiple cell functions including energy distribution through the cell, energy/heat modulation, reactive oxygen species (ROS) regulation, calcium homeostasis, and apoptosis control. Recently, evidence is accumulating for a direct participation of mitochondria in stem cell proliferation and/or differentiation. All these functions suggest that mutations in either nuclear or mitochondrial DNA may induce serious cell impairments, and there is now evidence of more than 200 mtDNA mutations responsible for human pathologies. Moreover, mitochondria are, simultaneously, the main producer and target of ROS and, thus, multiple mitochondrial diseases are related to ROSinduced mitochondrial injuries. Among these, neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), inflammatory diseases such as sepsis, and aging itself, are caused or accompanied by ROS-induced mitochondrial dysfunctions. With regard to its action spectrum as an antioxidant, melatonin may be regarded as a firstchoice agent for preventing and/or reducing the excess of ROS, thereby maintaining mitochondrial homeostasis. Multiple in vitro and in vivo experiments have shown the protective role of melatonin on mitochondrial physiology, yielding a significant improvement in those diseases in which energy supply to the cell had been compromised. New lines of evidence suggest the participation of mitochondria in stem cell proliferation and differentiation, and preliminary data support the role of melatonin in these processes. This review accounts for the multiple functions of mitochondria and the mechanisms involved in the numerous beneficial effects of melatonin to maintain mitochondrial homeostasis.

Cell (patho)physiology of magnesium

2007 ◽  
Vol 114 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Federica I. Wolf ◽  
Valentina Trapani
Keyword(s):  
Energy Metabolism ◽  
Dynamic Environment ◽  
Biological Functions ◽  
Cellular Functions ◽  
Intracellular Magnesium ◽  
The Road ◽  
Cell Functions ◽  
Growth Energy

There is an unsettled debate about the role of magnesium as a ‘chronic regulator’ of biological functions, as opposed to the well-known role for calcium as an ‘acute regulator’. New and old findings appear to delineate an increasingly complex and important role for magnesium in many cellular functions. This review summarizes the available evidence for a link between the regulation of intracellular magnesium availability and the control of cell growth, energy metabolism and death, both in healthy and diseased conditions. A comprehensive view is precluded by technical difficulties in tracing magnesium within a multicompartment and dynamic environment like the cell; nevertheless, the last few years has witnessed encouraging progress towards a better characterization of magnesium transport and its storage or mobilization inside the cell. The latest findings pave the road towards a new and deeper appreciation of magnesium homoeostasis and its role in the regulation of essential cell functions.

scholarly journals Regulation of Epithelial Cell Functions by the Osmolality and Hydrostatic Pressure Gradients: A Possible Role of the Tight Junction as a Sensor

2019 ◽  
Vol 20 (14) ◽  
pp. 3513 ◽  
Author(s):  
Shinsaku Tokuda ◽  
Alan S. L. Yu
Keyword(s):  
Cell Proliferation ◽  
Hydrostatic Pressure ◽  
Tight Junction ◽  
External Environment ◽  
Transepithelial Transport ◽  
Pressure Gradients ◽  
Cell Functions ◽  
Pathological Conditions ◽  
Extracellular Environment

Epithelia act as a barrier to the external environment. The extracellular environment constantly changes, and the epithelia are required to regulate their function in accordance with the changes in the environment. It has been reported that a difference of the environment between the apical and basal sides of epithelia such as osmolality and hydrostatic pressure affects various epithelial functions including transepithelial transport, cytoskeleton, and cell proliferation. In this paper, we review the regulation of epithelial functions by the gradients of osmolality and hydrostatic pressure. We also examine the significance of this regulation in pathological conditions especially focusing on the role of the hydrostatic pressure gradient in the pathogenesis of carcinomas. Furthermore, we discuss the mechanism by which epithelia sense the osmotic and hydrostatic pressure gradients and the possible role of the tight junction as a sensor of the extracellular environment to regulate epithelial functions.

The photoreceptor cytoskeleton visualized

1992 ◽  
Vol 50 (1) ◽  
pp. 480-481
Author(s):  
Beth Burnside
Keyword(s):  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Polarization ◽  
Synaptic Proteins ◽  
Cell Functions ◽  
Vertebrate Photoreceptor ◽  
Numerous Cell ◽  
Turn Over

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 138-142 ◽  
Author(s):  
R. Morishita ◽  
S. Nakamura ◽  
Y. Nakamura ◽  
M. Aoki ◽  
A. Moriguchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Potential Role ◽  
Specific Growth ◽  
Endothelial Damage ◽  
Specific Growth Factor ◽  
Hepatocyte Growth
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