Research ExplorerPublicationsLow density lipoprotein receptor-related protein 1 (LRP1) mo...

Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes

Standard

Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes. / Nakajima, Chikako; Kulik, Akos; Frotscher, Michael; Herz, Joachim; Schäfer, Michael; Bock, Hans H; May, Petra.

In: J BIOL CHEM, Vol. 288, No. 30, 26.07.2013, p. 21909-23.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Nakajima, C, Kulik, A, Frotscher, M, Herz, J, Schäfer, M, Bock, HH & May, P 2013, 'Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes', J BIOL CHEM, vol. 288, no. 30, pp. 21909-23. https://doi.org/10.1074/jbc.M112.444364

APA

Nakajima, C., Kulik, A., Frotscher, M., Herz, J., Schäfer, M., Bock, H. H., & May, P. (2013). Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes. J BIOL CHEM, 288(30), 21909-23. https://doi.org/10.1074/jbc.M112.444364

Vancouver

Nakajima C, Kulik A, Frotscher M, Herz J, Schäfer M, Bock HH et al. Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes. J BIOL CHEM. 2013 Jul 26;288(30):21909-23. https://doi.org/10.1074/jbc.M112.444364

Bibtex

@article{0a70f4684e8b45aa865a4b6efc8b6d42,
title = "Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes",
abstract = "The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes γ-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pull-down and chromatin immunoprecipitation (ChIP) assays showed no direct interaction between the LRP1-ICD and either CREB or target gene promoters. On the other hand, NMDA-induced degradation of the postsynaptic scaffold protein PSD-95 was impaired in the absence of LRP1, whereas its ubiquitination was increased, indicating that LRP1 influences the composition of postsynaptic protein complexes. Accordingly, NMDA-induced internalization of the AMPA receptor subunit GluA1 was impaired in LRP1-deficient neurons. These results show a role of LRP1 in the regulation and turnover of synaptic proteins, which may contribute to the reduced dendritic branching and to the neurological phenotype observed in the absence of LRP1.",
keywords = "Amyloid Precursor Protein Secretases, Animals, Blotting, Western, Cell Survival, Cells, Cultured, Embryo, Mammalian, Female, Gene Expression, Guanylate Kinase, Male, Membrane Proteins, Mice, Mice, Knockout, Mice, Transgenic, N-Methylaspartate, Neurons, Protein Binding, Protein Subunits, Receptors, LDL, Receptors, N-Methyl-D-Aspartate, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Synapses, Synaptosomes, Tumor Suppressor Proteins",
author = "Chikako Nakajima and Akos Kulik and Michael Frotscher and Joachim Herz and Michael Sch{\"a}fer and Bock, {Hans H} and Petra May",
year = "2013",
month = jul,
day = "26",
doi = "10.1074/jbc.M112.444364",
language = "English",
volume = "288",
pages = "21909--23",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

RIS

TY - JOUR

T1 - Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes

AU - Nakajima, Chikako

AU - Kulik, Akos

AU - Frotscher, Michael

AU - Herz, Joachim

AU - Schäfer, Michael

AU - Bock, Hans H

AU - May, Petra

PY - 2013/7/26

Y1 - 2013/7/26

N2 - The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes γ-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pull-down and chromatin immunoprecipitation (ChIP) assays showed no direct interaction between the LRP1-ICD and either CREB or target gene promoters. On the other hand, NMDA-induced degradation of the postsynaptic scaffold protein PSD-95 was impaired in the absence of LRP1, whereas its ubiquitination was increased, indicating that LRP1 influences the composition of postsynaptic protein complexes. Accordingly, NMDA-induced internalization of the AMPA receptor subunit GluA1 was impaired in LRP1-deficient neurons. These results show a role of LRP1 in the regulation and turnover of synaptic proteins, which may contribute to the reduced dendritic branching and to the neurological phenotype observed in the absence of LRP1.

AB - The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes γ-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pull-down and chromatin immunoprecipitation (ChIP) assays showed no direct interaction between the LRP1-ICD and either CREB or target gene promoters. On the other hand, NMDA-induced degradation of the postsynaptic scaffold protein PSD-95 was impaired in the absence of LRP1, whereas its ubiquitination was increased, indicating that LRP1 influences the composition of postsynaptic protein complexes. Accordingly, NMDA-induced internalization of the AMPA receptor subunit GluA1 was impaired in LRP1-deficient neurons. These results show a role of LRP1 in the regulation and turnover of synaptic proteins, which may contribute to the reduced dendritic branching and to the neurological phenotype observed in the absence of LRP1.

KW - Amyloid Precursor Protein Secretases

KW - Animals

KW - Blotting, Western

KW - Cell Survival

KW - Cells, Cultured

KW - Embryo, Mammalian

KW - Female

KW - Gene Expression

KW - Guanylate Kinase

KW - Male

KW - Membrane Proteins

KW - Mice

KW - Mice, Knockout

KW - Mice, Transgenic

KW - N-Methylaspartate

KW - Neurons

KW - Protein Binding

KW - Protein Subunits

KW - Receptors, LDL

KW - Receptors, N-Methyl-D-Aspartate

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - Synapses

KW - Synaptosomes

KW - Tumor Suppressor Proteins

U2 - 10.1074/jbc.M112.444364

DO - 10.1074/jbc.M112.444364

M3 - SCORING: Journal article

C2 - 23760271

VL - 288

SP - 21909

EP - 21923

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 30

ER -