INVESTIGADORES
BELFORTE Juan Emilio
artículos
Título:
eIF2alpha Phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general translation.
Autor/es:
JIANG Z, BELFORTE JE, LU Y, YABE Y, PICKEL J, SMITH CB, JE HS, LU B, NAKAZAWA K.
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Año: 2010 p. 2582 - 2594
ISSN:
0270-6474
Resumen:
Protein synthesis inhibitor antibiotics are widely used to produce amnesia, and have been recognized to inhibit general or global mRNA
translation in the basic translational machinery. For instance, anisomycin interferes with protein synthesis by inhibiting peptidyl transferase
or the 80S ribosomal function. Therefore, de novo general or global protein synthesis has been thought to be necessary for
long-term memory formation. However, it is unclear which mode of translation gene-specific translation or general/global translation
is actually crucial for the memory consolidation process in mammalian brains. Here, we generated a conditional transgenic mouse
strain in which double-strand RNA-dependent protein kinase (PKR)-mediated phosphorylation of eIF2, a key translation initiation
protein, was specifically increased in hippocampal CA1 pyramidal cells by the chemical inducer AP20187. Administration of AP20187
significantly increased activating transcription factor 4 (ATF4) translation and concomitantly suppressed CREB-dependent pathways in
CA1 cells; this led to impaired hippocampal late-phase LTP and memory consolidation, with no obvious reduction in general translation.
Conversely, inhibition of general translation by low-dose anisomycin failed to block hippocampal-dependent memory consolidation.
Together, these results indicated that CA1-restricted genetic manipulation of particular mRNA translations is sufficient to impair the
consolidation and that consolidation of memories in CA1 pyramidal cells through eIF2 dephosphorylation depends more on transcription/
translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance
of gene-specific translations for hippocampal memory consolidation.de novo general or global protein synthesis has been thought to be necessary for
long-term memory formation. However, it is unclear which mode of translation gene-specific translation or general/global translation
is actually crucial for the memory consolidation process in mammalian brains. Here, we generated a conditional transgenic mouse
strain in which double-strand RNA-dependent protein kinase (PKR)-mediated phosphorylation of eIF2, a key translation initiation
protein, was specifically increased in hippocampal CA1 pyramidal cells by the chemical inducer AP20187. Administration of AP20187
significantly increased activating transcription factor 4 (ATF4) translation and concomitantly suppressed CREB-dependent pathways in
CA1 cells; this led to impaired hippocampal late-phase LTP and memory consolidation, with no obvious reduction in general translation.
Conversely, inhibition of general translation by low-dose anisomycin failed to block hippocampal-dependent memory consolidation.
Together, these results indicated that CA1-restricted genetic manipulation of particular mRNA translations is sufficient to impair the
consolidation and that consolidation of memories in CA1 pyramidal cells through eIF2 dephosphorylation depends more on transcription/
translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance
of gene-specific translations for hippocampal memory consolidation., a key translation initiation
protein, was specifically increased in hippocampal CA1 pyramidal cells by the chemical inducer AP20187. Administration of AP20187
significantly increased activating transcription factor 4 (ATF4) translation and concomitantly suppressed CREB-dependent pathways in
CA1 cells; this led to impaired hippocampal late-phase LTP and memory consolidation, with no obvious reduction in general translation.
Conversely, inhibition of general translation by low-dose anisomycin failed to block hippocampal-dependent memory consolidation.
Together, these results indicated that CA1-restricted genetic manipulation of particular mRNA translations is sufficient to impair the
consolidation and that consolidation of memories in CA1 pyramidal cells through eIF2 dephosphorylation depends more on transcription/
translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance
of gene-specific translations for hippocampal memory consolidation. dephosphorylation depends more on transcription/
translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance
of gene-specific translations for hippocampal memory consolidation.