The F3/11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180 (original) (raw)
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Interactions of developing neurons with the extracellular matrix
The Journal of Neuroscience, 1994
The differentiation and morphogenesis of neural tissues involves a diversity of interactions between neural cells and their environment. Many potentially important interactions occur with the extracellular matrix (ECM), a complex association of extracellular glycoproteins organized into aggregates and polymers. In this article, we discuss recent findings on neuronal interactions with the ECM and their roles in neural cell migration and neurite growth. First, we examine the expression and putative functions of the molecules of the neural ECM. Second, we discuss cell surface molecules that mediate neural interactions with ECM components. Last, we address proteoglycans (PGs), a diverse class of glycoproteins, present both as ECM components and as cell surface molecules, which may mediate neural interactions with their environment. The best-understood cellular interactions with the ECM are adhesive, mediated by binding between specific cell surface molecules and cell binding domains of ECM components (Strittmater and Fishman, 199 1; Damsky and Werb, 1992). Cellsubstratum adhesion is necessary for major cell movements of neuron morphogenesis, that is, the migrations of neural cells and their precursors and the migratory behavior ofgrowth cones at the extending tips of axons and dendrites. As cells move, adhesive molecules at the surface of the leading edge of a migrating cell or growth cone bind to ligands on other cell surfaces or ECM components. These bonds stabilize filopodia and lamellipodia, and, in some cases, provide anchorage against which cytoskeletal filaments, associated with the plasma membrane, exert forces to pull the cell or growth cone forward. Thus, ECM has been primarily viewed as an adhesive substratum to provide traction for migrating cells and to stabilize the position and, perhaps, the state of differentiation of nonmotile cells. However, the interactions between neural cells and the ECM are not longer regarded as only adhesive or mechanical. Two points are now clear. First, some of these interactions are definitely not adhesive, but, rather, they may even be antiadhesive (Chiquet-Ehrismann, 199 1). Second, evidence has accumulated to indicate that the cell surface molecules that mediate cell-cell and cell-ECM interactions (immunoglobulin superfamily, cad-Preparation of this review was supported by NIH Grants HDI 9950 and NS28807
Contact inhibition of growth cone motility during neural development and regeneration
Seminars in Neuroscience, 1991
The potential importance of contact inhibition for neural development and regeneration has only recently been recognised. Growth cones have been shown to undergo abrupt collapse following contact with various cell types in vitro, including other neurons, and the collapse phenomenon is now being exploited to isolate and characterise the relevant molecules. Identifying the underlying mechanisms, which may involve ligand-receptor interactions, will be necessary for a full understanding of both axon guidance and the failure of axons to regenerate in the CNS of higher vertebrates. Key words : contact inhibition / glycoconjugates / growth cone / nerve regeneration / neural development CONTACT inhibition of cell movement has been a familiar phenomenon since its original description in fibroblast cultures by Abercrombie and Heaysman in 1954. 1 Only more recently, however, have neurobiologists begun seriously to consider the possibility that contact inhibition at nerve endings may play an important role in shaping the developing and mature nervous system. 2 It is easy to suggest (as we do below) that developmental processes such as axon guidance, synapse formation and synapse elimination may involve inhibitory as well as adhesive interactions. It is also possible that the failure of regeneration in the mature CNS of higher vertebrates results, at least in part, from inhibitory interactions between axons and their immediate environment. Our purpose here is to show that there is now strong evidence that inhibitory or repulsive interactions are implicated in neural development and regeneration, that this is apparent in several different experimental systems, and that the way is now open for a detailed understanding of the molecular mechanisms involved .
Responses to cell contacts between growth cones, neurites and ganglionic non-neuronal cells
Journal of Neurocytology, 1980
The motility of growth cones of embryonic peripheral neurons is not inhibited by contact with the surfaces of neurites or of non-neuronal cells. Rather, growth cones and microspikes adhere to other cell surfaces and often respond with forward movement and elongation in contact with other cells, as they do on adhesive surfacesin vitro. Furthermore, non-neuronal cells do not display contact inhibition when they contact growth cones or neurites. If anything, surface motility and ruffling is stimulated by contact with a neuronal cell surface and some non-neuronal cells prefer to migrate along neurites rather than on the surface of the culture dish. These observations on the contact behaviour of cells from peripheral nerve ganglia imply that the surfaces of embryonic neurons differ from those of non-neuronal cells in that the neuronal surfaces do not elicit the typical contact inhibition response.
An emerging link between cytoskeletal dynamics and cell adhesion molecules in growth cone guidance
Current Opinion in Neurobiology, 1998
It has become increasingly evident that growth cone guidance depends on the concerted actions of cytoskeletal proteins, molecular motors and cell adhesion molecules. Recent studies suggest that modulation of coupling between extracellular substrates and intracellular cytoskeletal networks via cell surface receptors is an important mechanism for regulating directed neuronal growth.
Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors
Proceedings of the National Academy of Sciences, 2004
Fibroblasts in 2D cultures differ dramatically in behavior from those in the 3D environment of a multicellular organism. However, the basis of this disparity is unknown. A key difference is the spatial arrangement of anchored extracellular matrix (ECM) receptors to the ventral surface in 2D cultures and throughout the entire surface in 3D cultures. Therefore, we asked whether changing the topography of ECM receptor anchorage alone could invoke a morphological response. By using polyacrylamide-based substrates to present anchored fibronectin or collagen on dorsal cell surfaces, we found that well spread fibroblasts in 2D cultures quickly changed into a bipolar or stellate morphology similar to fibroblasts in vivo. Cells in this environment lacked lamellipodia and large actin bundles and formed small focal adhesions only near focused sites of protrusion. These responses depend on substrate rigidity, calcium ion, and, likely, the calcium-dependent protease calpain. We suggest that fibroblasts respond to both spatial distribution and mechanical input of anchored ECM receptors. Changes in cell shape may in turn affect diverse cellular activities, including gene expression, growth, and differentiation, as shown in numerous previous studies.
Journal of Neurobiology, 1992
Mechiinisms of cell-cell recognition and structural changes of growth cones (g.c.) and target membranes during contact formation are poorly understood. To examine these issues, we obtained a high magnification, realtime record of stable contact formation in cultured cells from the hippocampal C A I area in the newborn rat. We used differential interference contrast (DIC) optics coupled to a video microscope for periods of over 24 h of continuous time-lapse recording. Our goal was to observe the sequential changes exhibited by afferent and target cells as they form a stable contact. Understanding the process of how stable contacts are made is important because such contacts are the first step in synapse formation. Four principal observations emerged from our study: (I) The target cell was receptive to a contact on a specific patch on its surface defined by the presence of lamellae and filopodia. This specific patch (named target site) was invariably present on the target cell surface before the time the growth cone arrived. (2) Stable adhesion between filopodia on the two cells initiated events leading to cell-cell contact formation. Specifically, the remaining filopodia on the growth cone and target cell were redirected toward the adhering filopodia, and the growth cone size decreased dramatically. (3) The axonal process then grew at a significantly accelerated rate (up to 50 times its baseline growth rate). (4) In addition, a number of observations were obtained on axonal turns towards the target cell, induction of target sites, and architectural remodelling of cells after the formation of a new contact. Our findings indicate that in this neuronal system, filopodia are the means used by cells to interact a t stages prior to and during contact formation. We speculate that the molecules involved in cell recognition and the machinery that initiates contact formation are embedded in the fine structure of filopodia. Finally, our results provide possible clues a s to some of the stages that may be involved in synapse formation in the mammalian central nervous system.
The Journal of cell biology, 1998
Dynamic cytoskeletal rearrangements are involved in neuronal growth cone motility and guidance. To investigate how cell surface receptors translate guidance cue recognition into these cytoskeletal changes, we developed a novel in vitro assay where beads, coated with antibodies to the immunoglobulin superfamily cell adhesion molecule apCAM or with purified native apCAM, replaced cellular substrates. These beads associated with retrograde F-actin flow, but in contrast to previous studies, were then physically restrained with a microneedle to simulate interactions with noncompliant cellular substrates. After a latency period of approximately 10 min, we observed an abrupt increase in bead-restraining tension accompanied by direct extension of the microtubule-rich central domain toward sites of apCAM bead binding. Most importantly, we found that retrograde F-actin flow was attenuated only after restraining tension had increased and only in the bead interaction axis where preferential mic...
Mobilization of the cell adhesion glycoprotein F3/contactin to axonal surfaces is activity dependent
European Journal of Neuroscience, 2001
F3/contactin is a cell adhesion/recognition molecule of the immunoglobulin superfamily implicated in axonal growth. We examined its subcellular distribution and mobilization to the cell surface in oxytocin-(OT-) secreting neurons, which express it throughout life and the axons of which undergo activity-dependent remodelling. This was performed in hypothalamic organotypic slice cultures containing OT neurons with properties of adult neurosecretory cells. Immunocytochemistry and immunoblot analysis con®rmed that OT neurons express high levels of F3/contactin in vitro. Light and confocal microscopy of cultures that underwent double immuno¯uorescence after ®xation showed F3/contactin immunoreactivity throughout the cytoplasm of OT somata, dendrites and axons, and also in non-OT axons and in putative synaptic boutons which contacted OT neurons. By contrast, after treatment of live cultures with anti-F3/contactin antibodies followed by double immuno¯uorescence for the glycoprotein and OT, F3/contactin immunoreactivity was visible only on the surface of axons, whether or not OT-immunoreactivity was present. Because of its glycosylphosphatidyl-inositol (GPI) linkage, F3/contactin can occur in a membrane-bound or soluble form. As seen from immunocytochemistry of live cells and immunoblot analysis, treatment of cultures with a GPI-speci®c phospholipase C (GPI-PLC) resulted in loss of F3/contactin immunoreactivity from all cell surfaces. F3/contactin immunoreactivity reappeared on axonal surfaces within 5 h after enzyme washout. Such re-expression was accelerated by neuronal activity facilitation (by K + depolarization or g-aminobutyric acid (GABA)-A receptor blockade with bicuculline) and inhibited by neuronal activity repression [by blockade of Ca 2+ channels with Mn 2+ , Na + channels with tetrodotoxin (TTX) or excitatory inputs with glutamate antagonists]. Our observations establish therefore that F3/contactin surface expression in hypothalamic neurons is polarized to the axons where it occurs mainly in a GPI-linked form. We also provide direct evidence that externalization of F3/contactin depends on Ca 2+ entry and neuronal electrical activity. Taken together with our earlier ®nding that the glycoprotein is localized in neurosecretory granules, we demonstrate that F3/contactin is mobilized to the axonal surface via the activity-dependent regulated pathway, thus arriving at the correct place and time to intervene in activity-dependent remodelling of axons.