Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

Honjo, Yasuko; Nakagawa, Shinichi; Takeichi, Masatoshi

doi:10.1046/j.1365-2443.2000.00327.x

Cited by 23 publications

(13 citation statements)

References 37 publications

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“…2). These findings confirm a previous report that ␤-catenin does not bind directly to PSD-93 (Honjo et al, 2000). Thus, although cytoplasmic ␤-catenin, which binds to APC, is targeted for rapid degradation in the Wnt pathway, our data indicate that APC, ␤-catenin, and PSD-93 are sequestered and form a complex in the psd in vivo.…”

Section: Apc and Its Binding Partners Form A Complex In The Postsynapsupporting

confidence: 91%

Neuronal Nicotinic Synapse Assembly Requires the Adenomatous Polyposis Coli Tumor Suppressor Protein

Temburni¹,

Rosenberg²,

Pathak³

et al. 2004

J. Neurosci.

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Normal cognitive and autonomic functions require nicotinic synaptic signaling. Despite the physiological importance of these synapses, little is known about molecular mechanisms that direct their assembly during development. We show here that the tumor-suppressor protein adenomatous polyposis coli (APC) functions in localizing ␣3-nicotinic acetylcholine receptors (nAChRs) to neuronal postsynaptic sites. Our quantitative confocal microscopy studies indicate that APC is selectively enriched at cholinergic synapses; APC surface clusters are juxtaposed to synaptic vesicle clusters and colocalize with ␣3-nAChRs but not with the neighboring synaptic glycine receptors or perisynaptic ␣7-nAChRs on chick ciliary ganglion (CG) neurons. We identify PSD (postsynaptic density)-93, ␤-catenin, and microtubule end binding protein EB1 as APC binding partners. PSD-93 and ␤-catenin are also enriched at ␣3-nAChR postsynaptic sites. EB1 shows close proximity to and partial overlap with ␣3-nAChR and APC surface clusters. We tested the role of APC in neuronal nicotinic synapse assembly by using retroviral-mediated in vivo overexpression of an APC dominant-negative (APC-dn) peptide to block the interaction of endogenous APC with both EB1 and PSD-93 during synapse formation in CG neurons. The overexpressed APC-dn led to dramatic decreases in ␣3-nAChR surface levels and clusters. Effects were specific to ␣3-nAChR postsynaptic sites; synaptic glycine receptor and perisynaptic ␣7-nAChR clusters were not altered. In addition, APC-dn also reduced surface membrane-associated clusters of PSD-93 and EB1. The results show that APC plays a key role in organizing excitatory cholinergic postsynaptic specializations in CG neurons. We identify APC as the first nonreceptor protein to function in localizing nAChRs to neuronal synapses in vivo.

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Section: Apc and Its Binding Partners Form A Complex In The Postsynapsupporting

confidence: 91%

Neuronal Nicotinic Synapse Assembly Requires the Adenomatous Polyposis Coli Tumor Suppressor Protein

Temburni¹,

Rosenberg²,

Pathak³

et al. 2004

J. Neurosci.

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“…This antibody is originally raised against a PDZ domain of PSD95/SAP90 (Honjo et al, 2000;Jourdi et al, 2003). Our immunoblotting revealed that this antibody recognizes, at least, more than 10 molecules with different sizes, some of which corresponded to PSD-95 and SAP97 (Fig.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 95%

“…Our previous study indicates that a BDNF-triggered increase in total PDZ protein content results in an increase in pan-PDZ-positive postsynaptic sites on dendrites (Jourdi et al, 2003). The expression of PDZ proteins was, therefore, assessed by immunocytochemistry using the anti-pan-PDZ antibody (mAb K28/86.2) that is suggested to recognize multiple members of the PSD-95 family including PSD-95, SAP97 and Chapsyn 110/PSD-93 (Honjo et al, 2000). EGF treatment influenced pan-PDZ immunoreactivity along the dendrites.…”

Section: Reduction In Pan-pdz Immunoreactivity In Egf-treated Long-tementioning

confidence: 99%

ErbB1 receptor ligands attenuate the expression of synaptic scaffolding proteins, GRIP1 and SAP97, in developing neocortex

Yokomaku¹,

Jourdi²,

Kakita³

et al. 2005

Neuroscience

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Scaffolding proteins containing postsynaptic density-95/discs large/zone occludens-1 (PDZ) domains interact with synaptic receptors and cytoskeletal components and are therefore implicated in synaptic development and plasticity. Little is known, however, about what regulates the expression of PDZ proteins and how the levels of these proteins influence synaptic development. Here, we show that ligands for epidermal growth factor receptors (ErbB1) decrease a particular set of PDZ proteins and negatively influence synaptic formation or maturation. In short-term neocortical cultures, concentrations of epidermal growth factor and amphiregulin (2-9 pM) decreased the expression of glutamate receptor interacting protein 1 (GRIP1) and synapseassociated protein 97 kDa (SAP97) without affecting postsynaptic density-95 (PSD-95) levels and glial proliferation. In long-term cultures, epidermal growth factor treatment resulted in a decrease in the frequency of pan-PDZ-immunoreactive aggregates on dendritic processes. A similar activity on the same PDZ proteins was observed in the developing neocortex following epidermal growth factor administration to rat neonates. Immunoblotting revealed that administered epidermal growth factor from the periphery activated brain ErbB1 receptors and decreased GRIP1 and SAP97 protein levels in the neocortex. Laser-confocal imaging indicated that epidermal growth factor administration suppressed the formation of pan-PDZ-immunoreactive puncta and dispersed those structures in vivo as well. These findings revealed a novel negative activity of ErbB1 receptor ligands that attenuates the expression of the PDZ proteins and inhibits postsynaptic maturation in developing neocortex. KeywordsEGFR; HER1; amphiregulin; synaptic elimination; cerebral cortex; postsynaptic; schizophrenia Proteins carrying PDZ (postsynaptic density-95/discs large/zone occludens-1) domains are referred to as PDZ proteins, which have a modular organization and often function as scaffolding proteins. Recent studies have indicated that these proteins interact with various types of synaptic proteins, such as ion channels, signal transducers, and cytoskeletal thereby playing an important role in the functional localization of these proteins by linking the receptors to the cytoskeleton (Valtschanoff and Weinberg, 2001;Lei et al., 2001;Petersen et al., 2003;Lin et al., 2004). SAP97 binds to AMPARs and similarly modulates their subcellular dynamics (Leonard et al., 1998;Valtschanoff et al., 2000;Wu et al., 2002;Ko et al., 2003). Thus, PDZ proteins perform key roles in synaptic function and plasticity. Little is known, however, about the molecular regulators of PDZ protein expression during synaptic development. Growth factors and neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neuregulin-1 (NRG1), influence synaptic formation and maturation in part by regulating the expression of glutamate and acetylcholine receptors and controlling their subcellular localizations (Ozaki et al., 1997;Narisawa-Saito et al., 19...

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“…These include cytoskeletal proteins, scaffold proteins, signaling proteins, proteases, and receptors. Expression of dominantnegative cadherins in hippocampal neurons suppresses the normal recruitment of synapsin and PSD-95 to excitatory synapses (354), and treatment of retinal neurons with blocking antibodies against cadherin 6B impairs the subcellular localization of PSD-95 (136). The N-cadherin-␤-catenin complexes bind to an AMPA receptor (GluR2/3) (81, 239), and this association restricts the lateral diffusion of GluR2 (239,291).…”

Section: Synapse Differentiation and Signalingmentioning

confidence: 99%

Cadherins in Brain Morphogenesis and Wiring

Hirano

Takeichi

2012

Physiological Reviews

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260

312

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LHirano S, Takeichi M. Cadherins in Brain Morphogenesis and Wiring. Physiol Rev 92: 597-634, 2012; doi:10.1152/physrev.00014.2011 -dependent cell-cell adhesion molecules that play critical roles in animal morphogenesis. Various cadherin-related molecules have also been identified, which show diverse functions, not only for the regulation of cell adhesion but also for that of cell proliferation and planar cell polarity. During the past decade, understanding of the roles of these molecules in the nervous system has significantly progressed. They are important not only for the development of the nervous system but also for its functions and, in turn, for neural disorders. In this review, we discuss the roles of cadherins and related molecules in neural development and function in the vertebrate brain.

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Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

Abstract: Background: Synaptic junctions have cadherin±catenin complexes, but their functions are poorly understood. Using retinal neurones, we investigated the role of this adhesion machinery in synaptic organization.

Cited by 23 publications

References 37 publications

Neuronal Nicotinic Synapse Assembly Requires the Adenomatous Polyposis Coli Tumor Suppressor Protein

Neuronal Nicotinic Synapse Assembly Requires the Adenomatous Polyposis Coli Tumor Suppressor Protein

ErbB1 receptor ligands attenuate the expression of synaptic scaffolding proteins, GRIP1 and SAP97, in developing neocortex

Cadherins in Brain Morphogenesis and Wiring

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