Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha(2)-macroglobulin

Title

Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha(2)-macroglobulin

Creator

Chiabrando G A; Sanchez M C; Skornicka E L; Koo P H

Publisher

Journal of Neuroscience Research

Date

2002
2002-10

Description

Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein closely related to human alpha(2)-macroglobulin (alpha(2)M). It has been demonstrated that monoamine-activated forms of human and rat alpha(2)M and rat alpha(2)M can bind to TrkA and, respectively, inhibit and stimulate NGF-promoted neurite outgrowth, Trk phosphorylation, and intracellular signal transduction in PC12 cells. However, the effect of PZP on neurons is unknown, and the molecular mechanism of neuroinhibition by monoamine-activated alpha(2)M is still unclear. In this report, we show that methylamine-activated PZP (MA-PZP), like MA-alpha(2)M, inhibits in a dose-dependent way the NGF-promoted neurite extension and TrkA phosphorylation in PC12 cells. On the other hand, normal PZP (N-PZP) had little or no effect. In addition, the inhibitory effect of activated alpha-macroglobulins (alphaMs) was reversible upon its removal from the cell culture. In addition, PZP, as well as alpha(2)M, is neuroinhibitory without being directly cytotoxic. It is known that the activated alphaMs bind to the multiligand receptor termed low-density lipoprotein receptor-related protein (LRP) and that the receptor-associated protein (RAP) specifically blocks uptake of all known LRP ligands. To investigate the potential role of LRP in neuromodulation by activated PZP/alpha(2)M, the effect of RAP on the neuroinhibitory activities of these alphaMs was also studied. Data presented here show that RAP blocked the neurite- and Trk- inhibitory activities of both MA-PZP and MA-alpha(2)M whereas RAP itself had no neuromodulatory effect. Hence, we conclude that these data suggest that the LRP receptor and its alphaM ligands may play a role in regulating Trk receptors. (C) 2002 Wiley-Liss, Inc.

Subject

phosphorylation; Signal transduction; receptors; Neurosciences & Neurology; binding; gene-expression; Signal transduction; alpha-2-macroglobulin; alpha-macroglobulin; alpha-macroglobulins; amyloid precursor protein; cytosolic adapter; low-density lipoprotein receptor-related protein; lrp; neurological diseases; rat alpha-1-macroglobulin; trk; Trk regulation

Identifier

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

57-64

Issue

1

Volume

70

Citation

Chiabrando G A; Sanchez M C; Skornicka E L; Koo P H, “Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha(2)-macroglobulin,” NEOMED Bibliography Database, accessed June 13, 2021, https://neomed.omeka.net/items/show/8889.

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