Context-dependent spindle pole focusing

2018 ◽  
Vol 62 (6) ◽  
pp. 803-813 ◽  
Author(s):  
Lori Borgal ◽  
James G. Wakefield
Keyword(s):  
Protein Complexes ◽  
Cell Types ◽  
Spindle Pole ◽  
Mitotic Apparatus ◽  
Spindle Formation ◽  
Complex Process ◽  
Cellular Context ◽  
Polar Spindle ◽  
Context Dependent ◽  
Different Cell Types

The formation of a robust, bi-polar spindle apparatus, capable of accurate chromosome segregation, is a complex process requiring the co-ordinated nucleation, sorting, stabilization and organization of microtubules (MTs). Work over the last 25 years has identified protein complexes that act as functional modules to nucleate spindle MTs at distinct cellular sites such as centrosomes, kinetochores, chromatin and pre-existing MTs themselves. There is clear evidence that the extent to which these different MT nucleating pathways contribute to spindle mass both during mitosis and meiosis differs not only between organisms, but also in different cell types within an organism. This plasticity contributes the robustness of spindle formation; however, whether such plasticity is present in other aspects of spindle formation is less well understood. Here, we review the known roles of the protein complexes responsible for spindle pole focusing, investigating the evidence that these, too, act co-ordinately and differentially, depending on cellular context. We describe relationships between MT minus-end directed motors dynein and HSET/Ncd, depolymerases including katanin and MCAK, and direct minus-end binding proteins such as nuclear-mitotic apparatus protein, ASPM and Patronin/CAMSAP. We further explore the idea that the focused spindle pole acts as a non-membrane bound condensate and suggest that the metaphase spindle pole be treated as a transient organelle with context-dependent requirements for function.

scholarly journals Assembly of multiple dystrobrevin-containing complexes in the kidney

2000 ◽  
Vol 113 (15) ◽  
pp. 2715-2724
Author(s):  
N.Y. Loh ◽  
S.E. Newey ◽  
K.E. Davies ◽  
D.J. Blake
Keyword(s):  
Skeletal Muscle ◽  
Protein Complexes ◽  
Cell Types ◽  
Epithelial Morphogenesis ◽  
Basal Region ◽  
Molecular Architecture ◽  
Renal Epithelial Cells ◽  
Specific Antibodies ◽  
Different Cell Types ◽  
Deficient Mice

Dystrophin is the key component in the assembly and maintenance of the dystrophin-associated protein complex (DPC) in skeletal muscle. In kidney, dystroglycan, an integral component of the DPC, is involved in kidney epithelial morphogenesis, suggesting that the DPC is important in linking the extracellular matrix to the internal cytoskeleton of kidney epithelia. Here, we have investigated the molecular architecture of dystrophin-like protein complexes in kidneys from normal and dystrophin-deficient mice. Using isoform-specific antibodies, we show that the different cell types that make up the kidney maintain different dystrophin-like complexes. These complexes can be broadly grouped according to their dystrobrevin content: beta-dystrobrevin containing complexes are present at the basal region of renal epithelial cells, whilst alpha-dystrobrevin-1 containing complexes are found in endothelial and smooth muscle cells. Furthermore, these complexes are maintained even in the absence of all dystrophin isoforms. Thus our data suggest that the functions and assembly of the dystrophin-like complexes in kidney differ from those in skeletal muscle and implicate a protein other than dystrophin as the primary molecule in the assembly and maintenance of kidney complexes. Our findings also provide a possible explanation for the lack of kidney pathology in Duchenne muscular dystrophy patients and mice lacking all dystrophin isoforms.

scholarly journals The effect of the signalling scheme on the robustness of pattern formation in development

2012 ◽  
Vol 2 (4) ◽  
pp. 465-486 ◽  
Author(s):  
Hye-Won Kang ◽  
Likun Zheng ◽  
Hans G. Othmer
Keyword(s):  
Pattern Formation ◽  
Reaction Diffusion ◽  
Threshold Value ◽  
Cell Types ◽  
State Variable ◽  
Complex Process ◽  
Spatially Distributed ◽  
Stochastic Reaction ◽  
Different Cell Types ◽  
Parameter Values

Pattern formation in development is a complex process which involves spatially distributed signals called morphogens that influence gene expression and thus the phenotypic identity of cells. Usually different cell types are spatially segregated, and the boundary between them may be determined by a threshold value of some state variable. The question arises as to how sensitive the location of such a boundary is to variations in properties, such as parameter values, that characterize the system. Here, we analyse both deterministic and stochastic reaction-diffusion models of pattern formation with a view towards understanding how the signalling scheme used for patterning affects the variability of boundary determination between cell types in a developing tissue.

Wound healing and local neuroendocrine regulation in the injured liver

2008 ◽  
Vol 10 ◽  
Author(s):  
Mohammad R. Ebrahimkhani ◽  
Ahmed M. Elsharkawy ◽  
Derek A. Mann
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Neuroendocrine System ◽  
Therapeutic Interventions ◽  
Antifibrotic Therapy ◽  
Complex Process ◽  
Wound Healing Response ◽  
Fibrotic Scar ◽  
Different Cell Types

The hepatic wound-healing response is a complex process involving many different cell types and factors. It leads to the formation of excessive matrix and a fibrotic scar, which ultimately disrupts proper functioning of the liver and establishes cirrhosis. Activated hepatic myofibroblasts, which are derived from cells such as hepatic stellate cells (HSCs), play a key role in this process. Upon chronic liver injury, there is an upregulation in the local neuroendocrine system and it has recently been demonstrated that activated HSCs express specific receptors and respond to different components of this system. Neuroendocrine factors and their receptors participate in a complex network that modulates liver inflammation and wound healing, and controls the development and progression of liver fibrosis. The first part of this review provides an overview of the molecular mechanisms governing hepatic wound healing. In the second section, we explore important components of the hepatic neuroendocrine system and their recently highlighted roles in HSC biology and hepatic fibrogenesis. We discuss the therapeutic interventions that are being developed for use in antifibrotic therapy.

scholarly journals Vascular Calcification in Chronic Kidney Disease: Diversity in the Vessel Wall

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 404
Author(s):  
Prabhatchandra Dube ◽  
Armelle DeRiso ◽  
Mitra Patel ◽  
Dhanushya Battepati ◽  
Bella Khatib-Shahidi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Complex Process ◽  
Cardiovascular Morbidity And Mortality ◽  
Depth Analysis ◽  
Multiple Cell ◽  
Different Cell Types

Vascular calcification (VC) is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). VC is a complex process expressing similarity to bone metabolism in onset and progression. VC in CKD is promoted by various factors not limited to hyperphosphatemia, Ca/Pi imbalance, uremic toxins, chronic inflammation, oxidative stress, and activation of multiple signaling pathways in different cell types, including vascular smooth muscle cells (VSMCs), macrophages, and endothelial cells. In the current review, we provide an in-depth analysis of the various kinds of VC, the clinical significance and available therapies, significant contributions from multiple cell types, and the associated cellular and molecular mechanisms for the VC process in the setting of CKD. Thus, we seek to highlight the key factors and cell types driving the pathology of VC in CKD in order to assist in the identification of preventative, diagnostic, and therapeutic strategies for patients burdened with this disease.

A CELLULAR AUTOMATON TO MODEL THE DEVELOPMENT OF PRIMARY SHOOT MERISTEMS OF ARABIDOPSIS THALIANA

2007 ◽  
Vol 05 (02b) ◽  
pp. 641-650 ◽  
Author(s):  
ILYA R. AKBERDIN ◽  
EVGENIY A. OZONOV ◽  
VICTORIA V. MIRONOVA ◽  
NADEZDA A. OMELYANCHUK ◽  
VITALY A. LIKHOSHVAI ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Cellular Automaton ◽  
Gene Networks ◽  
Cell Types ◽  
Shoot Meristem ◽  
Regulatory Mechanisms ◽  
Developmental Gene ◽  
Complex Process ◽  
Different Cell Types ◽  
Shoot Meristems

Development of organisms is a very complex process in which a lot of gene networks of different cell types are integrated. Development of a cellular automaton (Ermentrout and Edelshtein-Keshet, J Theor Biol160:97–133, 1993) that models the morphodynamics of different cell types is the first step in understanding and analysis of the regulatory mechanisms underlying the functioning of developmental gene networks. A model of a cellular automaton has been developed, which simulates the embryonic development of shoot meristem in Arabidopsis thaliana. The model adequately describes the basic stages in development of this organ in wild and mutant types.

scholarly journals Emerging concepts in biliary repair and fibrosis

2017 ◽  
Vol 313 (2) ◽  
pp. G102-G116 ◽  
Author(s):  
Luca Fabris ◽  
Carlo Spirli ◽  
Massimiliano Cadamuro ◽  
Romina Fiorotto ◽  
Mario Strazzabosco
Keyword(s):  
Biliary Tree ◽  
Alagille Syndrome ◽  
Cell Types ◽  
Current Debate ◽  
Joint Control ◽  
New Concepts ◽  
Complex Process ◽  
Reparative Process ◽  
Mixed Origin ◽  
Different Cell Types

Chronic diseases of the biliary tree (cholangiopathies) represent one of the major unmet needs in clinical hepatology and a significant knowledge gap in liver pathophysiology. The common theme in cholangiopathies is that the target of the disease is the biliary tree. After damage to the biliary epithelium, inflammatory changes stimulate a reparative response with proliferation of cholangiocytes and restoration of the biliary architecture, owing to the reactivation of a variety of morphogenetic signals. Chronic damage and inflammation will ultimately result in pathological repair with generation of biliary fibrosis and clinical progression of the disease. The hallmark of pathological biliary repair is the appearance of reactive ductular cells, a population of cholangiocyte-like epithelial cells of unclear and likely mixed origin that are able to orchestrate a complex process that involves a number of different cell types, under joint control of inflammatory and morphogenetic signals. Several questions remain open concerning the histogenesis of reactive ductular cells, their role in liver repair, their mechanism of activation, and the signals exchanged with the other cellular elements cooperating in the reparative process. This review contributes to the current debate by highlighting a number of new concepts derived from the study of the pathophysiology of chronic cholangiopathies, such as congenital hepatic fibrosis, biliary atresia, and Alagille syndrome.

scholarly journals Eph/Ephrin-Based Protein Complexes: The Importance of cis Interactions in Guiding Cellular Processes

2022 ◽  
Vol 8 ◽  
Author(s):  
Alessandra Cecchini ◽  
D. D. W. Cornelison
Keyword(s):  
Tyrosine Kinases ◽  
Cellular Response ◽  
Protein Complexes ◽  
Cell Types ◽  
Linear Process ◽  
Diverse Range ◽  
Ephb Receptor ◽  
Cellular Context ◽  
Associated Proteins ◽  
And Migration

Although intracellular signal transduction is generally represented as a linear process that transmits stimuli from the exterior of a cell to the interior via a transmembrane receptor, interactions with additional membrane-associated proteins are often critical to its success. These molecules play a pivotal role in mediating signaling via the formation of complexes in cis (within the same membrane) with primary effectors, particularly in the context of tumorigenesis. Such secondary effectors may act to promote successful signaling by mediating receptor-ligand binding, recruitment of molecular partners for the formation of multiprotein complexes, or differential signaling outcomes. One signaling family whose contact-mediated activity is frequently modulated by lateral interactions at the cell surface is Eph/ephrin (EphA and EphB receptor tyrosine kinases and their ligands ephrin-As and ephrin-Bs). Through heterotypic interactions in cis, these molecules can promote a diverse range of cellular activities, including some that are mutually exclusive (cell proliferation and cell differentiation, or adhesion and migration). Due to their broad expression in most tissues and their promiscuous binding within and across classes, the cellular response to Eph:ephrin interaction is highly variable between cell types and is dependent on the cellular context in which binding occurs. In this review, we will discuss interactions between molecules in cis at the cell membrane, with emphasis on their role in modulating Eph/ephrin signaling.

scholarly journals Synchronized cardiac impulses emerge from multi-scale, heterogeneous local calcium signals within and among cells of heart pacemaker tissue

2020 ◽  
Author(s):  
Rostislav Bychkov ◽  
Magdalena Juhaszova ◽  
Kenta Tsutsui ◽  
Christopher Coletta ◽  
Michael D. Stern ◽  
...  
Keyword(s):  
Neuronal Networks ◽  
Sinoatrial Node ◽  
Cell Types ◽  
Low Resolution ◽  
Impulse Generation ◽  
Multi Scale ◽  
Complex Processes ◽  
Self Organized ◽  
Complex Process ◽  
Different Cell Types

ABSTRACTBackgroundThe current paradigm of Sinoatrial Node (SAN) impulse generation: (i) is that full-scale action potentials (APs) of a common frequency are initiated at one site and are conducted within the SAN along smooth isochrones; and (ii) does not feature fine details of Ca2+ signalling present in isolated SAN cells, in which small subcellular, subthreshold local Ca2+ releases (LCRs) self-organize to generate cell-wide APs.ObjectivesTo study subcellular Ca2+ signals within and among cells comprising the SAN tissue.MethodsWe combined immunolabeling with a novel technique to detect the occurrence of LCRs and AP-induced Ca2+ transients (APCTs) in individual pixels (chonopix) across the entire mouse SAN images.ResultsAt high magnification, Ca2+ signals appeared markedly heterogeneous in space, amplitude, frequency, and phase among cells comprising an HCN4+/CX43- cell meshwork. The signalling exhibited several distinguishable patterns of LCR/APCT interactions within and among cells. Apparently conducting rhythmic APCTs of the meshwork were transferred to a truly conducting HCN4-/CX43+ network of straited cells via narrow functional interfaces where different cell types intertwine, i.e. the SAN anatomical/functional unit. At low magnification, the earliest APCT of each cycle occurred within a small area of the HCN4 meshwork and subsequent APCT appearance throughout SAN pixels was discontinuous.ConclusionsWe have discovered a novel, microscopic Ca2+ signalling paradigm of SAN operation that has escaped detection using low-resolution, macroscopic tissue isochrones employed in prior studies: APs emerge from heterogeneous subcellular subthreshold Ca2+ signals, resembling multiscale complex processes of impulse generation within clusters of neurons in neuronal networks.Condensed abstractBy combining immunolabeling with a novel optical technique we detected markedly heterogenous Ca2+signals within and among cell clusters of an HCN4+/CX43- meshwork in mouse sinoatrial node. These Ca2+ signals self-organized and transferred, throughout the node, to projections from an HCN4-/CX43+ network connected to a highly organized, rapidly conducting part of the CX43+ network. Thus, APs emerge from heterogeneous, subthreshold Ca2+ signaling not detected in low-resolution macroscopic isochrones. Our discovery requires a fundamental paradigm shift from concentric impulse propagation initiated within a leading site, to a multiscale/complex process, resembling the emergence of organized signals from heterogeneous local signals within neuronal networks.

scholarly journals Signalling Properties of Inositol Polyphosphates

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5281
Author(s):  
Tania Maffucci ◽  
Marco Falasca
Keyword(s):  
Enzymatic Activity ◽  
Protein Complexes ◽  
Cell Types ◽  
Pharmacological Interventions ◽  
Inositol Polyphosphates ◽  
Cellular Processes ◽  
New Information ◽  
Different Cell Types

Several studies have identified specific signalling functions for inositol polyphosphates (IPs) in different cell types and have led to the accumulation of new information regarding their cellular roles as well as new insights into their cellular production. These studies have revealed that interaction of IPs with several proteins is critical for stabilization of protein complexes and for modulation of enzymatic activity. This has not only revealed their importance in regulation of several cellular processes but it has also highlighted the possibility of new pharmacological interventions in multiple diseases, including cancer. In this review, we describe some of the intracellular roles of IPs and we discuss the pharmacological opportunities that modulation of IPs levels can provide.

The alpha 6 beta 1 (VLA-6) and alpha 6 beta 4 protein complexes: tissue distribution and biochemical properties

1990 ◽  
Vol 96 (2) ◽  
pp. 207-217 ◽  
Author(s):  
A. Sonnenberg ◽  
C.J. Linders ◽  
J.H. Daams ◽  
S.J. Kennel
Keyword(s):  
Monoclonal Antibodies ◽  
Protein Complexes ◽  
Cell Types ◽  
Biochemical Properties ◽  
Immunoperoxidase Staining ◽  
Tissue Sections ◽  
Adult Mice ◽  
Carcinoma Cell Lines ◽  
Different Cell Types ◽  
Human And Mouse

A member of the integrin family, the alpha 6 beta 4 complex was previously identified on human and mouse carcinoma cell lines by using a rat monoclonal antibody to alpha 6. Here we describe two monoclonal antibodies that recognize epitopes on the beta 4 subunit of the human and mouse alpha 6 beta 4 complexes. The monoclonal antibodies against beta 4 were able to preclear alpha 6 beta 4, but not alpha 6 beta 1 from cell line extracts. A substantial fraction of the total beta 4 subunits present on the cell surface was not associated with alpha 6, as it could not be removed by anti-alpha 6 antibodies, but remained precipitable with anti-beta 4 antibodies. There was no evidence for novel alpha subunits associated with beta 4. The alpha 6 subunit consists of disulfide-linked heavy and light chains. The variability in size of these two chains from different cell types is largely due to differences in modifications of N-linked glycans. Additional heterogeneity may be caused by differential proteolytic cleavage of the alpha 6 precursor. Immunoperoxidase staining of tissue sections of neonatal and adult mice revealed that beta 4 expression is limited to epithelial tissues and peripheral nerves. The alpha 6 subunit has a wider distribution that includes all tissues and cells stained by antibodies against beta 4. Cells and tissue that are positive for alpha 6, but negative for beta 4, may express the alpha 6 beta 1 complex.

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