scholarly journals A nutrient sentinel stands guard outside the cell

2018 ◽  
Vol 293 (43) ◽  
pp. 16951-16952 ◽  
Author(s):  
Davide Vigetti ◽  
Ilaria Caon ◽  
Alberto Passi

Nutrient sensing is a critical cell function that regulates survival and growth by adjusting metabolism. During nutrient shortage, autophagy enables the recycling of major cellular components to prevent cell death. Understanding the mechanisms that trigger and control autophagy is of fundamental importance, as this degradative pathway plays a pivotal role in many diseases. Gubbiotti et al. report the identification of a new player, the proteoglycan decorin, which functions as a nutrient sensor in the extracellular matrix and controls autophagy in the heart.

2005 ◽  
Vol 360 (1464) ◽  
pp. 2255-2258 ◽  
Author(s):  
Laura Berliocchi ◽  
Daniele Bano ◽  
Pierluigi Nicotera

Cell death programmes are generally defined by biochemical/genetic routines that are linked to their execution and by the appearance of more or less typical morphological features. However, in pathological settings death signals may engage complex and interacting lethal pathways, some of which are common to different cells, whereas others are linked to a specific tissue and differentiation pattern. In neurons, death programmes can be spatially and temporally segregated. Most importantly physiological Ca 2+ signals are essential for cell function and survival. On the other hand, Ca 2+ overload or perturbations of intracellular Ca 2+ compartmentalization can activate or enhance mechanisms leading to cell death. An imbalance between Ca 2+ influx and efflux from cells is the initial signal leading to Ca 2+ overload and death of ischaemic neurons or cardiomyocytes. Alterations of intracellular Ca 2+ storage can integrate with death signals that do not initially require Ca 2+ , to promote processing of cellular components and death by apoptosis or necrosis. Finally, Ca 2+ can directly activate catabolic enzymes such as proteases, phospholipases and nucleases that directly cause cell demise and tissue damage.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinyoung Kim ◽  
Kihyoun Park ◽  
Min Jung Kim ◽  
Hyejin Lim ◽  
Kook Hwan Kim ◽  
...  

AbstractWe have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.


2018 ◽  
Vol 9 ◽  
Author(s):  
Gorjana Rackov ◽  
Noemi Garcia-Romero ◽  
Susana Esteban-Rubio ◽  
Josefa Carrión-Navarro ◽  
Cristobal Belda-Iniesta ◽  
...  

2012 ◽  
Vol 92 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Sandra G. Velleman ◽  
Jonghyun Shin ◽  
Xuehui Li ◽  
Yan Song

Velleman, S. G., Shin, J., Li, X. and Song, Y. 2012. Review: The skeletal muscle extracellular matrix: Possible roles in the regulation of muscle development and growth. Can. J. Anim. Sci. 92: 1–10. Skeletal muscle fibers are surrounded by an extrinsic extracellular matrix environment. The extracellular matrix is composed of collagens, proteoglycans, glycoproteins, growth factors, and cytokines. How the extracellular matrix influences skeletal muscle development and growth is an area that is not completely understood at this time. Studies on myogenesis have largely been directed toward the cellular components and overlooked that muscle cells secrete a complex extracellular matrix network. The extracellular matrix modulates muscle development by acting as a substrate for muscle cell migration, growth factor regulation, signal transduction of information from the extracellular matrix to the intrinsic cellular environment, and provides a cellular structural architecture framework necessary for tissue function. This paper reviews extracellular matrix regulation of muscle growth with a focus on secreted proteoglycans, cell surface proteoglycans, growth factors and cytokines, and the dynamic nature of the skeletal muscle extracellular matrix, because of its impact on the regulation of muscle cell proliferation and differentiation during myogenesis.


2021 ◽  
Vol 28 ◽  
Author(s):  
Javier Rojo ◽  
Pedro M. Nieto ◽  
José Luis de Paz

: Langerin is a C-type Lectin expressed at the surface of Langerhans cells, which play a pivotal role in protecting organisms against pathogen infections. To address this aim, Langerin presents at least two recognition sites, one Ca2+-dependent and another one independent, capable of recognizing a variety of carbohydrate ligands. In contrast to other lectins, Langerin recognizes sulfated glycosaminoglycans (GAGs), a family of complex and heterogeneous polysaccharides present in the cell membrane and the extracellular matrix at the interphase generated in the trimeric form of Langerin but absent in the monomeric form. The complexity of these oligosaccharides has impeded the development of well-defined monodisperse structures to study these interaction processes. However, in the last few decades, an improvement of synthetic developments to achieve the preparation of carbohydrate multivalent systems mimicking the GAGs has been described. Despite all these contributions, very few examples are reported where the GAG multivalent structures are used to evaluate the interaction with Langerin. These molecules should pave the way to explore these GAG-Langerin interactions.


Development ◽  
2021 ◽  
Vol 148 (24) ◽  
Author(s):  
Samantha A. Russell ◽  
Kaitlin M. Laws ◽  
Greg J. Bashaw

ABSTRACT The Netrin receptor Frazzled/Dcc (Fra in Drosophila) functions in diverse tissue contexts to regulate cell migration, axon guidance and cell survival. Fra signals in response to Netrin to regulate the cytoskeleton and also acts independently of Netrin to directly regulate transcription during axon guidance in Drosophila. In other contexts, Dcc acts as a tumor suppressor by directly promoting apoptosis. In this study, we report that Fra is required in the Drosophila female germline for the progression of egg chambers through mid-oogenesis. Loss of Fra in the germline, but not the somatic cells of the ovary, results in the degeneration of egg chambers. Although a failure in nutrient sensing and disruptions in egg chamber polarity can result in degeneration at mid-oogenesis, these factors do not appear to be affected in fra germline mutants. However, similar to the degeneration that occurs in those contexts, the cell death effector Dcp-1 is activated in fra germline mutants. The function of Fra in the female germline is independent of Netrin and requires the transcriptional activation domain of Fra. In contrast to the role of Dcc in promoting cell death, our observations reveal a role for Fra in regulating germline survival by inhibiting apoptosis.


Development ◽  
1976 ◽  
Vol 36 (2) ◽  
pp. 225-245
Author(s):  
Robert M. Greene ◽  
Robert M. Pratt

Research on development of the secondary palate has, in the past, dealt primarily with morphological aspects of shelf elevation and fusion. The many factors thought to be involved in palatal elevation, such as fetal neuromuscular activity and growth of the cranial base and mandible, as well as production of extracellular matrix and contractile elements in the palate, are mostly based on gross, light microscopic, morphometric or histochemical observations. Recently, more biochemical procedures have been utilized to describe palatal shelf elevation. Although these studies strongly suggest that palatal extracellular matrix plays a major role in shelf movement, interpretation of these data remains difficult owing to the complexity of tissue interactions involved in craniofacial development. Shelf elevation does not appear to involve a single motive factor, but rather a coordinated interaction of all of the abovementioned developmental events. Further analysis of mechanisms of shelf elevation requires development of new, and refinement of existing, in vitro procedures. A system that enables one to examine shelf elevation in vitro would allow more meaningful analysis of the relative importance of the various components in shelf movement. Much more is known about fusion of the palatal shelves, owing in large part to in vitro studies. Fusion of the apposing shelves, both in vivo and in vitro, is dependent upon adhesion and cell death of the midline epithelial cells. Adhesion between apposing epithelial surfaces appears to involve epithelial cell surface macromolecules. Further analysis of palatal epithelial adhesion should be directed towards characterization of those cell surface components responsible for this adhesive interaction. Midline epithelial cells cease DNA synthesis 24–36 h before shelf elevation and contact, become active in the synthesis of cell surface glycoproteins, and subsequently manifest morphological signs of necrosis. Death of the midline epithelial cells is thought to involve a programmed, lysosomal-mediated autolysis. Information regarding the appearance, distribution and quantitation of epithelial hydrolytic enzymes is needed. The control mechanisms which regulate adhesiveness and cell death in the palatal epithelium are not fully understood. Although palatal epithelial-mesenchymal recombination experiments have demonstrated a close relationship between the underlying mesenchyme and the differentiating epithelium, the molecular mechanism of interaction remains unclear. Recently cyclic nucleotides have been implicated as possible mediators of palatal epithelial differentiation. The developing secondary palate therefore offers a system whereby one can probe a variety of developmental phenomena. Cellular adhesion, programmed cell death and epithelial- mesenchymal interactions are all amenable to both morphological as well as bio- chemical analysis. Although research in the field of secondary palate development has been extensive, there still remain many provocative questions relating to normal development of this structure.


2011 ◽  
Vol 54 (1) ◽  
pp. 182-191.e24 ◽  
Author(s):  
Richard D. Kenagy ◽  
Seung-Kee Min ◽  
Eileen Mulvihill ◽  
Alexander W. Clowes

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1444 ◽  
Author(s):  
Sun Hee Cho ◽  
Jeong In Kim ◽  
Cheol Sang Kim ◽  
Chan Hee Park ◽  
In Gi Kim

To date, many researchers have studied a considerable number of three-dimensional (3D) cotton-like electrospun scaffolds for tissue engineering, including the generation of bone, cartilage, and skin tissue. Although numerous 3D electrospun fibrous matrixes have been successfully developed, additional research is needed to produce 3D patterned and sophisticated structures. The development of 3D fibrous matrixes with patterned and sophisticated structures (FM-PSS) capable of mimicking the extracellular matrix (ECM) is important for advancing tissue engineering. Because modulating nano to microscale features of the 3D fibrous scaffold to control the ambient microenvironment of target tissue cells can play a pivotal role in inducing tissue morphogenesis after transplantation in a living system. To achieve this objective, the 3D FM-PSSs were successfully generated by the electrospinning using a directional change of the sharply inclined array collector. The 3D FM-PSSs overcome the current limitations of conventional electrospun cotton-type 3D matrixes of random fibers.


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