Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion protein to laminin γ1 chain

被引：100

作者：

Beraldo, Flavio H. ^{[1
,5
,6
]}

Arantes, Camila P. ^{[1
,2
]}

Santos, Tiago G. ^{[1
,3
]}

Machado, Cleiton F. ^{[1
,3
]}

Roffe, Martin ^{[4
]}

Hajj, Glaucia N. ^{[1
]}

Lee, Kil S. ^{[1
]}

Magalhaes, Ana C. ^{[5
,6
]}

Caetano, Fabiana A. ^{[5
,6
,8
]}

Mancini, Gabriel. L. ^{[1
]}

Lopes, Marilene H. ^{[1
]}

Americo, Tatiana A. ^{[9
]}

Magdesian, Margaret H. ^{[10
]}

Ferguson, Stephen S. G. ^{[5
,6
]}

Linden, Rafael ^{[9
]}

Prado, Marco A. M. ^{[5
,6
,7
]}

Martins, Vilma R. ^{[1
]}

机构：

[1] Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, Sao Paulo, Brazil

[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, Brazil

[3] Hosp AC Camargo Fund Antonio Prudente, Ctr Tratamento & Pesquisa, Sao Paulo, Brazil

[4] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, Brazil

[5] Univ Western Ontario, J Allyn Taylor Ctr Cell Biol, Mol Brain Res Grp, Robarts Res Inst, London, ON, Canada

[6] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada

[7] Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada

[8] Univ Fed Minas Gerais, Program Mol Pharmacol, Belo Horizonte, MG, Brazil

[9] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil

[10] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil

来源：

FASEB JOURNAL | 2011年 / 25卷 / 01期

基金：

巴西圣保罗研究基金会;

关键词：

GPI-anchored proteins; G-coupled protein receptors; signal transduction; multiprotein complexes; neurotrophic signals; STRESS-INDUCIBLE PROTEIN-1; CELLULAR PRION; PROMOTING DOMAIN; KDI-DOMAIN; CALCIUM; PHOSPHORYLATION; DIFFERENTIATION; INTERNALIZATION; IDENTIFICATION; TRAFFICKING;

D O I：

10.1096/fj.10-161653

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The prion protein (PrPC) is highly expressed in the nervous system, and its abnormal conformer is associated with prion diseases. PrPC is anchored to cell membranes by glycosylphosphatidylinositol, and transmembrane proteins are likely required for PrPC-mediated intracellular signaling. Binding of laminin (Ln) to PrPC modulates neuronal plasticity and memory. We addressed signaling pathways triggered by PrPC-Ln interaction in order to identify transmembrane proteins involved in the transduction of PrPC-Ln signals. The Ln gamma 1-chain peptide, which contains the Ln binding site for PrPC, induced neuritogenesis through activation of phospholipase C (PLC), Ca2+ mobilization from intracellular stores, and protein kinase C and extracellular signal-regulated kinase (ERK1/2) activation in primary cultures of neurons from wild-type, but not PrPC-null mice. Phage display, coimmunoprecipitation, and colocalization experiments showed that group I metabotropic glutamate receptors (mGluR1/5) associate with PrPC. Expression of either mGluR1 or mGluR5 in HEK293 cells reconstituted the signaling pathways mediated by PrPC-Ln gamma 1 peptide interaction. Specific inhibitors of these receptors impaired PrPC-Ln gamma 1 peptide-induced signaling and neuritogenesis. These data show that group I mGluRs are involved in the transduction of cellular signals triggered by PrPC-Ln, and they support the notion that PrPC participates in the assembly of multiprotein complexes with physiological functions on neurons.-Beraldo, F. H., Arantes, C. P., Santos, T. G., Machado, C. F., Roffe, M., Hajj, G. N., Lee, K. S., Magalhaes, A. C., Caetano, F. A., Mancini, G. L., Lopes, M. H., Americo, T. A., Magdesian, M. H., Ferguson, S. S. G., Linden, R., Prado, M. A. M., Martins, V. R. Metabotropic glutamate receptors trans-duce signals for neurite outgrowth after binding of the prion protein to laminin gamma 1 chain. FASEB J. 25, 265-279 (2011). www.fasebj.org

引用

页码：265 / 279

页数：15

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