Nectin-1 Binds and Signals through the Fibroblast Growth Factor Receptor

Bojesen, Kirsten Borup; Clausen, O. P. F.; Rohde, Kristian; Christensen, Christa Lykke; Zhang, Lanjun; Li, Shizhong; Køhler, Lene B.; Nielbo, Steen; Nielsen, Janne; Gjørlund, Michelle D.; Poulsen, Flemming M.; Bock, Elisabeth; Berezin, Vladimir

doi:10.1074/jbc.m112.345215

Cited by 32 publications

(28 citation statements)

References 51 publications

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“…Neuronal nectin-1 may bind functionally to nectin-1 to itself, to nectin-3 or to the fibroblast growth factor receptor (FGFR) [4], [55]. Nectin-3 and nectin-1 share a binding site on the first Immunoglobulin-like domain (V-domain) of nectin-1 [56], [57] and promote cellular and synaptic adhesion.…”

Section: Discussionmentioning

confidence: 99%

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

et al. 2013

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Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions.

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Section: Discussionmentioning

confidence: 99%

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

et al. 2013

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“…The oxifin1 peptide derived from CD200 mimicked its neuritogenic and survival-promoting effects [96]. Proteins of the cell adhesion molecule (CAM) family, such as nectin-1, can also bind and activate FGF receptors [97]. CAMs signal through FGF receptors by trans-homophilic/heterophilic interactions of CAMs on opposite cells.…”

Section: Targeting the Fgf Systemmentioning

confidence: 99%

“…Nectin-1 is prominently expressed in brain, including the hippocampus. Furthermore, nectide is a peptide derived from nectin-1 which can mimic its effects, including those on cell survival [97]. …”

Section: Targeting the Fgf Systemmentioning

confidence: 99%

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

Turner

Eren-Koçak

Inui³

et al. 2016

Seminars in Cell & Developmental Biology

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The role of the fibroblast growth factor (FGF) system in brain-related disorders has received considerable attention in recent years. To understand the role of this system in neurological and psychiatric disorders, it is important to identify the specific members of the FGF family that are implicated, their location and the various mechanisms they can be modulated. Each disorder appears to impact specific molecular players in unique anatomical locations, and all of these could conceivably become targets for treatment. In the last several years, the issue of how to target this system directly has become an area of increasing interest. To date, the most promising therapeutics are small molecule inhibitors and antibodies that modulate FGF receptor (FGFR) function. Beyond attempting to modify the primary players affected by a given brain disorder, it may prove useful to target molecules, such as membrane-bound or extracellular proteins that interact with FGF ligands or FGFRs to modulate signaling.

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“…Most of these studies were done in transfected cell lines overexpressing these proteins, and it still remains unknown whether these interactions are direct or indirect. The direct interaction was reported only between nectin-1 and the FGF receptor (47). In this report, it was shown that the third Ig module of nectin-1 directly interacts with the FGF receptor as estimated by surface plasmon resonance.…”

Section: Discussionmentioning

confidence: 73%

“…Nectin-4 serves as the entry receptor for measles virus (66,67). In addition, nectin-1 and nectin-3 cis-interact with the FGF receptor and the PDGF receptor, respectively (42,47). Therefore, the novel cell adhesion apparatus identified here may also serve as a platform for cellular signaling and play physiological and pathological roles not only in the mammary gland but also in other organs.…”

Section: Discussionmentioning

confidence: 85%

A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development

Kitayama

Mizutani

Maruoka

et al. 2016

Journal of Biological Chemistry

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Mammary gland development is induced by the actions of various hormones to form a structure consisting of collecting ducts and milk-secreting alveoli, which comprise two types of epithelial cells known as luminal and basal cells. These cells adhere to each other by cell adhesion apparatuses whose roles in hormone-dependent mammary gland development remain largely unknown. Here we identified a novel cell adhesion apparatus at the boundary between the luminal and basal cells in addition to desmosomes. This apparatus was formed by the trans-interaction between the cell adhesion molecules nectin-4 and nectin-1, which were expressed in the luminal and basal cells, respectively. Nectin-4 of this apparatus further cis-interacted with the prolactin receptor in the luminal cells to enhance the prolactin-induced prolactin receptor signaling for alveolar development with lactogenic differentiation. Thus, a novel nectin-mediated cell adhesion apparatus regulates the prolactin receptor signaling for mammary gland development.The adult mammary gland, consisting of collecting ducts and alveoli, is arranged in a bi-layer structure of inner luminal cells surrounded by basal myoepithelial cells, with the outermost side ensheathed by the basement membrane (1) (Fig. 1A). The luminal cells form a sheet by adhering to adjacent cells through cell adhesion apparatuses, including tight junctions (TJs), These cell adhesion apparatuses are composed of cell adhesion molecules (CAMs) and peripheral membrane proteins, which connect CAMs with cytoskeletal proteins, such as actin filaments (F-actin), intermediate filaments, and microtubules (5, 6). The major CAMs at AJs are classical cadherins and nectins (5, 6). Cadherins directly bind ␤-catenin, which interacts with ␣-catenin and is associated with F-actin, whereas nectins bind afadin and are associated with F-actin. The major CAMs at TJs are claudins, occludin, and junctional adhesion molecules (7). These CAMs bind zonula occludens (ZO)-1, ZO-2, and ZO-3 and are associated with F-actin. The major CAMs at desmosomes are desmosomal cadherins, which bind to plakoglobin and plakophilin and are associated with keratin intermediate filaments through desmoplakin (8). Gap junctions consist of connexons made up of six connexin proteins (9). In the mammary gland, these CAMs and their associated molecules have been identified and characterized (10), but nectins and afadin have not yet been investigated.The mammary gland develops from a thickening in the ventral skin during embryogenesis that grows into a rudimentary ductal tree before birth (11-13). The female mammary gland continues to develop in a hormone-independent manner until puberty following which hormones induce ductal elongation and branching. Elongation and branching of ducts along with alveolar development with lactogenic differentiation are induced by pregnancy. This development of the mammary gland during puberty and pregnancy are regulated by hormones, including estrogen, progesterone, and prolactin, and growth factors and cytokines, su...

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Nectin-1 Binds and Signals through the Fibroblast Growth Factor Receptor

Cited by 32 publications

References 51 publications

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders

A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development

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