scholarly journals Sugar Antennae for Guidance Signals: Syndecans and Glypicans Integrate Directional Cues for Navigating Neurons

2006 ◽  
Vol 6 ◽  
pp. 1024-1036 ◽  
Author(s):  
Christa Rhiner ◽  
Michael O. Hengartner
Keyword(s):  
Cell Surface ◽  
Axon Guidance ◽  
Neuronal Network ◽  
Neuronal Migration ◽  
Synapse Formation ◽  
Nerve Cells ◽  
Heparan Sulfate Proteoglycans ◽  
Vast Number ◽  
Guidance Cues

Attractive and repulsive signals guide migrating nerve cells in all directions when the nervous system starts to form. The neurons extend thin processes, axons, that connect over wide distances with other brain cells to form a complicated neuronal network. One of the most fascinating questions in neuroscience is how the correct wiring of billions of nerve cells in our brain is controlled. Several protein families are known to serve as guidance cues for navigating neurons and axons. Nevertheless, the combinatorial potential of these proteins seems to be insufficient to sculpt the entire neuronal network and the appropriate formation of connections. Recently, heparan sulfate proteoglycans (HSPGs), which are present on the cell surface of neurons and in the extracellular matrix through which neurons and axons migrate, have been found to play a role in regulating cell migration and axon guidance. Intriguingly, the large number of distinct modifications that can be put onto the sugar side chains of these PGs would in principle allow for an enormous diversity of HSPGs, which could help in regulating the vast number of guidance choices taken by individual neurons. In this review, we will focus on the role of the cell surface HSPGs syndecan and glypican and specific HS modifications in promoting neuronal migration, axon guidance, and synapse formation.

scholarly journals Targeting the SLIT/ROBO pathway in tumor progression: molecular mechanisms and therapeutic perspectives

2019 ◽  
Vol 11 ◽  
pp. 175883591985523 ◽  
Author(s):  
Zhengdong Jiang ◽  
Gang Liang ◽  
Ying Xiao ◽  
Tao Qin ◽  
Xin Chen ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Tumor Development ◽  
Tumor Promotion ◽  
Cancer Therapies ◽  
Malignant Cells ◽  
Robo Receptors

The SLITs (SLIT1, SLIT2, and SLIT3) are a family of secreted proteins that mediate positional interactions between cells and their environment during development by signaling through ROBO receptors (ROBO1, ROBO2, ROBO3, and ROBO4). The SLIT/ROBO signaling pathway has been shown to participate in axonal repulsion, axon guidance, and neuronal migration in the nervous system and the formation of the vascular system. However, the role of the SLIT/ROBO pathway has not been thoroughly clarified in tumor development. The SLIT/ROBO pathway can produce both beneficial and detrimental effects in the growth of malignant cells. It has been confirmed that SLIT/ROBO play contradictory roles in tumorigenesis. Here, we discuss the tumor promotion and tumor suppression roles of the SLIT/ROBO pathway in tumor growth, angiogenesis, migration, and the tumor microenvironment. Understanding these roles will help us develop more effective cancer therapies.

scholarly journals Syntenin-knock out reduces exosome turnover and viral transduction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rudra Kashyap ◽  
Marielle Balzano ◽  
Benoit Lechat ◽  
Kathleen Lambaerts ◽  
Antonio Luis Egea-Jimenez ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Intercellular Communication ◽  
Scaffold Protein ◽  
Heparan Sulfate Proteoglycans ◽  
Knock Out ◽  
Major Class ◽  
Endosomal Membranes ◽  
Viral Transduction

AbstractExosomal transfers represent an important mode of intercellular communication. Syntenin is a small scaffold protein that, when binding ALIX, can direct endocytosed syndecans and syndecan cargo to budding endosomal membranes, supporting the formation of intraluminal vesicles that compose the source of a major class of exosomes. Syntenin, however, can also support the recycling of these same components to the cell surface. Here, by studying mice and cells with syntenin-knock out, we identify syntenin as part of dedicated machinery that integrates both the production and the uptake of secreted vesicles, supporting viral/exosomal exchanges. This study significantly extends the emerging role of heparan sulfate proteoglycans and syntenin as key components for macromolecular cargo internalization into cells.

scholarly journals Expression and role of Galectin-3 in the postnatal development of the cerebellum

2018 ◽  
Author(s):  
Inés González-Calvo ◽  
Fekrije Selimi
Keyword(s):  
Synaptic Plasticity ◽  
Immune System ◽  
Purkinje Cell ◽  
Axon Guidance ◽  
Neuronal Migration ◽  
Neural Circuits ◽  
Related Protein ◽  
Galectin 3 ◽  
The Brain

AbstractMany proteins initially identified in the immune system play roles in neurogenesis, neuronal migration, axon guidance, synaptic plasticity and other processes related to the formation and refinement of neural circuits. Although the function of the immune-related protein Galectin-3 (LGALS3) has been extensively studied in the regulation of inflammation, cancer and microglia activation, little is known about its role in the development of the brain. In this study, we identified that LGALS3 is expressed in the developing postnatal cerebellum. More precisely, LGALS3 is expressed by cells in meninges and in the choroid plexus, and in subpopulations of astrocytes and of microglial cells in the cerebellar cortex. Analysis of Lgals3 knockout mice showed that Lgals3 is dispensable for the development of cerebellar cytoarchitecture and Purkinje cell excitatory synaptogenesis in the mouse.

scholarly journals The Role of Apoptotic Signaling in Axon Guidance

2018 ◽  
Vol 6 (4) ◽  
pp. 24 ◽  
Author(s):  
Riley Kellermeyer ◽  
Leah Heydman ◽  
Grant Mastick ◽  
Thomas Kidd
Keyword(s):  
Axon Guidance ◽  
Neurotrophic Factors ◽  
Tumor Suppressors ◽  
Growth Cones ◽  
Cytoskeletal Proteins ◽  
Guidance Cues ◽  
Cytoskeletal Dynamics ◽  
Protease Activation ◽  
Entire Trajectory

Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.

Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction

2005 ◽  
Vol 203 (1) ◽  
pp. 166-176 ◽  
Author(s):  
James J. Moon ◽  
Melissa Matsumoto ◽  
Shyam Patel ◽  
Luke Lee ◽  
Jun-Lin Guan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Endothelial Cell Migration

scholarly journals A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate Inhibits the Basal and Hsp90-Stimulated Migration and Invasion of Tumor Cells

2020 ◽  
Vol 11 (2) ◽  
pp. 39 ◽  
Author(s):  
Anastasiya V. Snigireva ◽  
Oleg S. Morenkov ◽  
Yuri Y. Skarga ◽  
Alexander V. Lisov ◽  
Zoya A. Lisova ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cells ◽  
Heat Shock Protein 90 ◽  
Synthetic Polymer ◽  
Heparan Sulfate Proteoglycans ◽  
Migration And Invasion ◽  
Dihydroxybenzoic Acid ◽  
Ht1080 Cells ◽  
Polymeric Conjugate

The extracellular cell surface-associated and soluble heat shock protein 90 (Hsp90) is known to participate in the migration and invasion of tumor cells. Earlier, we demonstrated that plasma membrane-associated heparan sulfate proteoglycans (HSPGs) bind the extracellular Hsp90 and thereby promote the Hsp90-mediated motility of tumor cells. Here, we showed that a conjugate of 2,5-dihydroxybenzoic acid with gelatin (2,5-DHBA–gelatin), a synthetic polymer with heparin-like properties, suppressed the basal (unstimulated) migration and invasion of human glioblastoma A-172 and fibrosarcoma HT1080 cells, which was accompanied by the detachment of a fraction of Hsp90 from cell surface HSPGs. The polymeric conjugate also inhibited the migration/invasion of cells stimulated by exogenous soluble native Hsp90, which correlated with the inhibition of the attachment of soluble Hsp90 to cell surface HSPGs. The action of the 2,5-DHBA–gelatin conjugate on the motility of A-172 and HT1080 cells was similar to that of heparin. The results demonstrate a potential of the 2,5-DHBA–gelatin polymer for the development of antimetastatic drugs targeting cell motility and a possible role of extracellular Hsp90 in the suppression of the migration and invasion of tumor cells mediated by the 2,5-DHBA–gelatin conjugate and heparin.

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