Binding of APC to the Human Homolog of the
            <b>
              <i>Drosophila</i>
            </b>
            Discs Large Tumor Suppressor Protein

Matsumine, Akihiko; Ogai, Akiko; Senda, Toshiya; Okumura, Nobuaki; Satoh, Kiyoshi; Baeg, Gyeong-Hun; Kawahara, Takuji; Kobayashi, Shigeru; Okada, Masato; Toyoshima, Kumao; Akiyama, Tetsu

doi:10.1126/science.272.5264.1020

Cited by 407 publications

(357 citation statements)

References 29 publications

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“…APC is required for agrin-induced clustering of muscle-type nAChRs in myotubes and localizes to the neuromuscular junction . APC is also concentrated at neuronal glutamatergic synapses (Matsumine et al, 1996;Yanai et al, 2000) and is required, in vitro, for clustering of PSD-95 that, in turn, clusters AMPA receptors (Shimomura et al, 2007). Interestingly, the APC binding partners IQGAP1 and PSD-93/-95 are also shared between nicotinic and glutamatergic synapses (this study) (Conroy et al, 2003;Parker et al, 2004;Nuriya et al, 2005;Sheng and Hoogenraad, 2007).…”

Section: Discussionmentioning

confidence: 62%

Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex

Rosenberg

Yang

Giovanni

et al. 2008

Molecular and Cellular Neuroscience

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The neuronal nicotinic synapse plays a central role in normal cognitive and autonomic function. Molecular mechanisms that direct the assembly of this synapse remain poorly defined, however. We show here that adenomatous polyposis coli (APC) organizes a multi-molecular complex that is essential for targeting α3*nAChRs to synapses. APC interaction with microtubule plus-end binding protein EB1 is required for α3*nAChR surface membrane insertion and stabilization. APC brings together EB1, the key cytoskeletal regulators macrophin and IQGAP1, and 14-3-3 adapter protein at nicotinic synapses. 14-3-3, in turn, links the α3-subunit to APC. This multi-molecular APC complex stabilizes the local microtubule and F-actin cytoskeleton and links postsynaptic components to the cytoskeleton-essential functions for controlling the molecular composition and stability of synapses. This work identifies macrophin, IQGAP1 and 14-3-3 as novel nicotinic synapse components and defines a new role for APC as an in vivo coordinator of nicotinic postsynaptic assembly in vertebrate neurons.

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Section: Discussionmentioning

confidence: 62%

Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex

Rosenberg

Yang

Giovanni

et al. 2008

Molecular and Cellular Neuroscience

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“…Several MAGUKs, such as ZO-1 [41], ZO-2 [42], ZO-3 [43], hDlg [44], MAGI-1 [23,26], MAGI-2/S-SCAM [45] and MAGI-3 [46] are localised to cellular tight junctions. However MAGI-1 was chosen as the model MAGUK in this study because of its wide tissue distribution [23,24].…”

Section: Discussionmentioning

confidence: 99%

Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

et al. 2006

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MAGI-1, a member of the MAGUK family of proteins, is shown to be rapidly cleaved during Fasinduced apoptosis in mouse 3T3 A31 cells, and in UV irradiation-and staurosporine-induced apoptosis in HaCaT cells. This generates a 97 kDa N-terminal fragment that dissociates from the cell membrane; a process that is largely prevented in the presence of the caspase inhibitor Z-VADfmk. In addition, we show that in vitro translated radiolabelled MAGI-1 is efficiently cleaved into 97 kDa and 68 kDa fragments by caspases-3 and -7 at physiological concentrations and mutating the MAGI-1 Asp 761 to Ala completely abolished the caspase-induced cleavage. was delayed during apoptosis, whereas other caspase-dependent processes such as nuclear condensation were not affected, suggesting that cell detachment is parallel to them. Thus, MAGI-1 cleavage appears to be an important step in the disassembly of cell-cell contacts during apoptosis.

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“…8 Moreover, APC is widely expressed in the brain as well as other tissues, and is involved in cell adhesion and neuronal function. 17,20 Several researches have reported that abnormalities of neural cell adhesion, neuronal function, and Wnt/Wingless exist in schizophrenia. [10][11][12][13][14][15]18,19,[23][24][25][26] Third, APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…The APC-DLG complex participates in the regulation of both cell cycle progression and neuronal function. 20 Kawasaki et al 21 suggested that the APC-ASEF complex (ASEF, a Rac-specific guanine nucleotide exchange factor) regulates the actin cytoskeletal network, cell morphology and migration, and neuronal function. Recently, it has been reported that the mouse tumor suppressor protein APC has a role in acetylcholine receptor clustering and that the Wnt/bcatenin pathway crosstalks with agrin signaling cascade during synapse formation.…”

mentioning

confidence: 99%

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

Cui

Jiang

et al. 2005

Mol Psychiatry

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The etiology of schizophrenia is unclear, although family, twin, and linkage studies implicate genetic factors. Here, we identified adenomatous polyposis coli (APC), a tumor suppressor gene, as a risk factor for schizophrenia. We compared leukocytic gene expression patterns of six pairs of patients with schizophrenia and healthy controls by microarray. APC expression levels were significantly increased in all patients compared to healthy controls. To confirm the findings of microarray analysis, we measured expression levels of APC in the leukocytes from 30 relapse patients taking antipsychotic medication, 29 first-episode drug-naïve patients, and 30 healthy controls using real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). APC expression levels were significantly increased in leukocytes of schizophrenics both taking and not taking antipsychotic medication and hence the increase of APC expression was not due to antipsychotic medication. APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. Further, we performed the transmission disequilibrium test (TDT) and TDT based on haplotypes to search for the association between schizophrenia and APC by examining 163 parent-offspring trios of Chinese descent. We analyzed three single-nucleotide polymorphisms (SNPs) (rs2229992, rs42427, rs465899) at the exon region of APC. TDT showed that the three SNPs are significantly associated with schizophrenia (TDT v 2 ¼ 4.23, Po0.05; 4.15, Po0.05; 8.49 Po0.01, respectively; HHRRv 2 ¼ 5.54, Po0.05; 4.40, Po0.05; 9.79, Po0.01, respectively). We found a significant association between the APC haplotypes from rs2229992-rs42427-rs465899 and schizophrenia (Global v 2 ¼ 44.376,df ¼ 7, Po0.001). The C-A-T haplotype has a frequency of more than 57% and has a strong association with schizophrenia (v 2 ¼ 15.04, Po0.001). These results indicate that the APC may be a candidate gene conferring susceptibility to schizophrenia and also may be associated with reduced vulnerability to cancer in schizophrenia.

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Binding of APC to the Human Homolog of the Drosophila Discs Large Tumor Suppressor Protein

Cited by 407 publications

References 29 publications

Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex

Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex

Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia

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