Experience-dependent decrease in synaptically localized Fra-1.
The Fos family of transcription factors has been repeatedly shown to participate in the long-term neural responses associated with a variety of physiological stimuli, including activity-dependent plastic processes. Quite recently, several transcription factors have been found in synaptic regions, localized in dendrites and presynaptic terminals. Here we show that the transcription factor Fos-related antigen-1 (Fra-1) was detected in synaptosomes (Syn) and synaptic plasma membrane (SPM) fractions from the rat cerebral cortex and hippocampus as a single band migrating with M(r) 42-43 kDa. The 55-kDa c-Fos protein was also detected in syn and SPM fractions. Conversely, the inducible 62-65-kDa c-Fos is present in nuclear fractions from metrazole-treated animals (positive control), but not in Syn or SPM fractions. Furthermore, no Fra-2, Fos B or c-Jun immunoreactivities were detected in these same synaptic regions. DNA-mobility shift assays showed the presence of specific AP-1 binding activity in synaptic protein extracts. Immunoelectronmicroscopic analysis of cortical and hippocampal tissues revealed that Fra-1 and Fos-like immunoreactivities are localized in association with presynaptic plasma membranes. One trial inhibitory avoidance training, a hippocampal-dependent task, is associated with a time-dependent decrease (-31%) in Fra-1, but not in 55-kDa c-Fos, levels in hippocampal SPM fractions. In hippocampal homogenates, we do not detect significant changes in Fra-1 immunoreactivity, suggesting that this behavioural experience is probably accompanied by a subcellular redistribution of Fra-1 protein. These results suggest that Fra-1 may participate in the communication between synapse and the nucleus and in experience-dependent hippocampal plasticity.
Paratcha
G
G
Instituto de Biologia Celular y Neurociencias Prof. Dr. Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 3 Piso, Buenos Aires 1121, Argentina.
de Stein
M L
ML
Szapiro
G
G
Lopez
M
M
Bevilaqua
L
L
Cammarota
M
M
de Iraldi
A P
AP
Izquierdo
I
I
Medina
J H
JH
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology*; D006624:Hippocampus / Q000166:cytology*; D015151:Immunoblotting; D008297:Male; D008568:Memory / Q000502:physiology; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000378:metabolism; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1