scholarly journals Endoglycan plays a role in axon guidance and neuronal migration by negatively regulating cell-cell adhesion

2018 ◽  
Author(s):  
Thomas Baeriswyl ◽  
Alexandre Dumoulin ◽  
Martina Schaettin ◽  
Georgia Tsapara ◽  
Vera Niederkofler ◽  
...  

SUMMARYCell migration and axon guidance are important steps in the formation of neural circuits. Both steps depend on the interactions between cell surface receptors and molecules on cells along the pathway. In addition to cell-cell adhesion, these molecular interactions provide guidance information. The fine-tuning of cell-cell adhesion is an important aspect of cell migration, axon guidance, and synapse formation.Here, we show that Endoglycan, a sialomucin, plays a role in axon guidance and cell migration in the central nervous system. In the absence of Endoglycan, commissural axons failed to properly navigate the midline of the spinal cord. In the developing cerebellum, a lack of Endoglycan prevented migration of Purkinje cells and resulted in a stunted growth of the cerebellar lobes. Taken together, these results support the hypothesis that Endoglycan acts as a ‘lubricant’, a negative regulator of cell-cell adhesion, in both commissural axon guidance and Purkinje cell migration.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Thomas Baeriswyl ◽  
Alexandre Dumoulin ◽  
Martina Schaettin ◽  
Georgia Tsapara ◽  
Vera Niederkofler ◽  
...  

Axon navigation depends on the interactions between guidance molecules along the trajectory and specific receptors on the growth cone. However, our in vitro and in vivo studies on the role of Endoglycan demonstrate that in addition to specific guidance cue – receptor interactions, axon guidance depends on fine-tuning of cell-cell adhesion. Endoglycan, a sialomucin, plays a role in axon guidance in the central nervous system of chicken embryos, but it is neither an axon guidance cue nor a receptor. Rather, Endoglycan acts as a negative regulator of molecular interactions based on evidence from in vitro experiments demonstrating reduced adhesion of growth cones. In the absence of Endoglycan, commissural axons fail to properly navigate the midline of the spinal cord. Taken together, our in vivo and in vitro results support the hypothesis that Endoglycan acts as a negative regulator of cell-cell adhesion in commissural axon guidance.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 118
Author(s):  
David de Agustín-Durán ◽  
Isabel Mateos-White ◽  
Jaime Fabra-Beser ◽  
Cristina Gil-Sanz

The neocortex is an exquisitely organized structure achieved through complex cellular processes from the generation of neural cells to their integration into cortical circuits after complex migration processes. During this long journey, neural cells need to establish and release adhesive interactions through cell surface receptors known as cell adhesion molecules (CAMs). Several types of CAMs have been described regulating different aspects of neurodevelopment. Whereas some of them mediate interactions with the extracellular matrix, others allow contact with additional cells. In this review, we will focus on the role of two important families of cell–cell adhesion molecules (C-CAMs), classical cadherins and nectins, as well as in their effectors, in the control of fundamental processes related with corticogenesis, with special attention in the cooperative actions among the two families of C-CAMs.


2002 ◽  
Vol 115 (9) ◽  
pp. 1837-1846 ◽  
Author(s):  
Sandra van Wetering ◽  
Jaap D. van Buul ◽  
Safira Quik ◽  
Frederik P. J. Mul ◽  
Eloise C. Anthony ◽  
...  

The integrity of the endothelium is dependent on cell-cell adhesion, which is mediated by vascular-endothelial (VE)-cadherin. Proper VE-cadherin-mediated homotypic adhesion is, in turn, dependent on the connection between VE-cadherin and the cortical actin cytoskeleton. Rho-like small GTPases are key molecular switches that control cytoskeletal dynamics and cadherin function in epithelial as well as endothelial cells. We show here that a cell-penetrating, constitutively active form of Rac (Tat-RacV12) induces a rapid loss of VE-cadherin-mediated cell-cell adhesion in endothelial cells from primary human umbilical veins (pHUVEC). This effect is accompanied by the formation of actin stress fibers and is dependent on Rho activity. However,transduction of pHUVEC with Tat-RhoV14, which induces pronounced stress fiber and focal adhesion formation, did not result in a redistribution of VE-cadherin or an overall loss of cell-cell adhesion. In line with this observation, endothelial permeability was more efficiently increased by Tat-RacV12 than by Tat-RhoV14. The loss of cell-cell adhesion, which is induced by Tat-RacV12, occurred in parallel to and was dependent upon the intracellular production of reactive oxygen species (ROS). Moreover, Tat-RacV12 induced an increase in tyrosine phosphorylation of a component the VE-cadherin-catenin complex, which was identified as α-catenin. The functional relevance of this signaling pathway was further underscored by the observation that endothelial cell migration, which requires a transient reduction of cell-cell adhesion, was blocked when signaling through ROS was inhibited. In conclusion, Rac-mediated production of ROS represents a previously unrecognized means of regulating VE-cadherin function and may play an important role in the (patho)physiology associated with inflammation and endothelial damage as well as with endothelial cell migration and angiogenesis.


2014 ◽  
Vol 74 (11) ◽  
pp. 3054-3066 ◽  
Author(s):  
Emi Tokuda ◽  
Toshiki Itoh ◽  
Junya Hasegawa ◽  
Takeshi Ijuin ◽  
Yukiko Takeuchi ◽  
...  

Author(s):  
W. Mark Saltzman

The external surface of the cell consists of a phospholipid bilayer which carries a carbohydrate-rich coat called the glycocalyx; ionizable groups within the glycocalyx, such as sialic acid (N-acetyl neuraminate), contribute a net negative charge to the cell surface. Many of the carbohydrates that form the glycocalyx are bound to membrane-associated proteins. Each of these components— phospholipid bilayer, carbohydrate-rich coat, membrane-associated protein—has distinct physicochemical characteristics and is abundant. Plasma membranes contain ∼50% protein, ∼45% lipid, and ∼5% carbohydrate by weight. Therefore, each component influences cell interactions with the external environment in important ways. Cells can become attached to surfaces. The surface of interest may be geometrically complex (for example, the surface of another cell, a virus, a fiber, or an irregular object), but this chapter will focus on adhesion between a cell and a planar surface. The consequences of cell–cell adhesion are considered further in Chapter 8 (Cell Aggregation and Tissue Equivalents) and Chapter 9 (Tissue Barriers to Molecular and Cellular Transport). The consequences of cell–substrate adhesion are considered further in Chapter 7 (Cell Migration) and Chapter 12 (Cell Interactions with Polymers). Since the growth and function of many tissue-derived cells required attachment and spreading on a solid substrate, the events surrounding cell adhesion are fundamentally important. In addition, the strength of cell adhesion is an important determinant of the rate of cell migration, the kinetics of cell–cell aggregation, and the magnitude of tissue barriers to cell and molecule transport. Cell adhesion is therefore a major consideration in the development of methods and materials for cell delivery, tissue engineering, and tissue regeneration. The most stable and versatile mechanism for cell adhesion involves the specific association of cell surface glycoproteins, called receptors, and complementary molecules in the extracellular space, called ligands. Ligands may exist freely in the extracellular space, they may be associated with the extracellular matrix, or they may be attached to the surface of another cell. Cell–cell adhesion can occur by homophilic binding of identical receptors on different cells, by heterophilic binding of a receptor to a ligand expressed on the surface of a different cell, or by association of two receptors with an intermediate linker. Cell–matrix adhesion usually occurs by heterophilic binding of a receptor to a ligand attached to an insoluble element of the extracellular matrix.


2020 ◽  
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Meagan Collins ◽  
...  

AbstractA cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. Using KRT19 knockout (KO) cells and cells where K19 expression was rescued, we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion of MCF7 cells. A loss of K19 resulted in a lower level of plakoglobin and internalization of E-cadherin in early and recycling endosomes. Inhibiting internalization restored cell-cell adhesion of KRT19 KO cells, suggesting E-cadherin internalization contributes to defective adhesion. Ultimately, while K19 inhibited cell migration, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell migration but provides growth and survival advantages for circulating tumor cells. These findings provide context-dependent roles of K19 during metastasis.


Cell Motility ◽  
2004 ◽  
pp. 101-116
Author(s):  
Jason S. Ehrlich ◽  
W. James Nelson ◽  
Marc D. H. Hansen

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