RGD Reference Report - Low density lipoprotein receptor-related protein (LRP1) regulates Rac1 and RhoA reciprocally to control Schwann cell adhesion and migration. - Rat Genome Database

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Low density lipoprotein receptor-related protein (LRP1) regulates Rac1 and RhoA reciprocally to control Schwann cell adhesion and migration.

Authors: Mantuano, Elisabetta  Jo, Minji  Gonias, Steven L  Campana, W Marie 
Citation: Mantuano E, etal., J Biol Chem. 2010 May 7;285(19):14259-66. doi: 10.1074/jbc.M109.085126. Epub 2010 Mar 2.
RGD ID: 13800550
Pubmed: (View Article at PubMed) PMID:20197276
DOI: Full-text: DOI:10.1074/jbc.M109.085126

LDL receptor-related protein (LRP1) is expressed by Schwann cells in vivo mainly after injury to the peripheral nervous system (PNS). Schwann cells in primary culture, which provide a model of Schwann cells in the injured PNS, also express abundant LRP1. Herein, we show that LRP1 gene-silencing or treatment with receptor-associated protein (RAP) promotes Schwann cell adhesion and inhibits cell migration on fibronectin. LRP1 gene-silencing also resulted in the formation of prominent focal adhesions and actin stress fibers. These changes, which were induced by loss of LRP1 expression or activity, were explained mechanistically by an increase in activated RhoA, coupled with a decrease in activated Rac1. Known LRP1 ligands, including matrix metalloprotease-9, tissue-type plasminogen activator, and alpha(2)-macroglobulin activated Rac1 in LRP1-expressing Schwann cells. An inhibitor of Rac1 activation promoted Schwann cell adhesion. Conversely, in cells in which LRP1 was silenced, a Rho kinase inhibitor promoted migration and inhibited adhesion. These results demonstrate that direct binding of ligands to LRP1 controls activation of small Rho family GTPases. The effects of LRP1 gene-silencing and RAP implicate autocrine pathways involving endogenously produced LRP1 ligands. Regulation of Schwann cell migration by LRP1 may be important in PNS injury.

Annotation

Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Lrp1  (LDL receptor related protein 1)


Additional Information