The interaction between prion protein and laminin modulates memory consolidation.
Cellular prion protein (PrPc) has a pivotal role in prion diseases. PrPc is a specific receptor for laminin (LN) gamma1 peptide and several lines of evidence indicate that it is also involved in neural plasticity. Here we investigated whether the interaction between PrPc and LN plays a role in rat memory formation. We found that post-training intrahippocampal infusion of PrPc-derived peptides that contain the LN binding site (PrPc163-182 and PrPc173-192) or of anti-PrPc or anti-LN antibodies that inhibit PrPc-LN interaction impaired inhibitory avoidance memory retention. The amnesic effect of anti-PrPc antibodies and PrPc173-192 peptide was reversed by co-infusion of a LN gamma1 chain-derived peptide containing the PrPc-binding site, suggesting that PrPc-LN interaction is indeed crucial for memory consolidation. In addition, PrPc173-192 peptide and anti-PrPc or anti-LN antibodies also inhibited the activation of hippocampal cAMP-dependent protein kinase A (PKA) and extracellular regulated kinase (ERK1/2), two kinases that mediate the up-regulation of signaling pathways needed for consolidation of inhibitory avoidance memory. Our findings show that, through its interaction with LN, hippocampal PrPc plays a critical role in memory processing and suggest that this role is mediated by activation of both PKA and ERK1/2 signaling pathways.
Coitinho
Adriana S
AS
Centro Universitário Feevale, Instituto de Ciências da Saúde, RS 239, 2755, 93352-000, Novo Hamburgo, RS, and Centro de Cirurgia de Epilepsia do Estado de Santa Catarina, Hospital Governador Celso Ramos, SC, Brazil.
Freitas
Adriana R O
AR
Lopes
Marilene H
MH
Hajj
Glaucia N M
GN
Roesler
Rafael
R
Walz
Roger
R
Rossato
Janine I
JI
Cammarota
Martin
M
Izquierdo
Ivan
I
Martins
Vilma R
VR
Brentani
Ricardo R
RR
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007797:Laminin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D007797:Laminin; D010446:Peptide Fragments; D018621:PrPC Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases