Par-4 is a synaptic protein that regulates neurite outgrowth by altering calcium homeostasis and transcription factor AP-1 activation.
*Intracellular Signaling Peptides and Proteins; Animals; Antibodies; Apoptosis Regulatory Proteins; Calcium Signaling/*physiology; Calcium/*metabolism; Carrier Proteins/genetics/immunology/*metabolism; Cell Compartmentation/physiology; Cerebral Cortex/cytology; Gene Expression/physiology; Hippocampus/cytology; Homeostasis/physiology; Inbred C57BL; Mice; Nerve Growth Factor/pharmacology; Neurites/*metabolism; Neurons/metabolism/ultrastructure; PC12 Cells; Rats; Synaptosomes/metabolism; Transcription Factor AP-1/*metabolism; Transcriptional Activation/drug effects/physiology; Transfection
Although Par-4 (prostate apoptosis response-4) is involved in initiation of neurodegenerative cascades associated with certain neurodegenerative disorders, normal physiological roles of Par-4 in neurons have remained elusive. It was recently reported that Par-4 protein levels could be regulated at translational level in synaptic terminals following apoptotic insults, suggesting that Par-4 might play a role in synaptic function. We report that Par-4 is a synaptic protein preferably localized in postsynaptic density (PSD). The expression of Par-4 in synaptosome preparations and PSDs are developmentally and regionally regulated. Synaptic Par-4 is enriched in the cerebral cortex and the hippocampus, but not in the cerebellum. In vitro as well as in vivo experiments demonstrate that the levels of synaptic Par-4 increase as the neurons mature. Overexpression of Par-4 in transfected PC12 cells inhibits nerve growth factor (NGF)-induced cellular differentiation and neurite outgrowth by a mechanism involving aberrant elevation of intracellular calcium levels and suppression of activation of the transcription factor AP-1. The actions of Par-4 were consistently blocked by co-expression of the dominant negative regulator of Par-4 activity (the leucine zipper domain of Par-4). Since the leucine zipper domain of Par-4 (Leu.zip) may mediate protein–protein interactions, the results indicate that the actions of Par-4 require its interaction with other protein(s) or dimerization with itself. These results suggest that Par-4 may play an important role in postsynaptic signal transduction and regulation of cellular pathways associated with cellular differentiation and neurite outgrowth. Identification of Par-4 as a novel synaptic protein may have significant implications in understanding the mechanisms of synaptic functions in physiological and pathological settings.
Guo Q; Xie J; Chang X; Zhang X; Du H
Brain research
2001
2001-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(01)02304-6" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(01)02304-6</a>
Synaptic activity-induced Ca(2+) signaling in avian cochlear nucleus magnocellularis neurons.
Animals; Calcium Signaling/*physiology; Chick Embryo; Chickens; Cochlear Nucleus/*metabolism; GABA-A/metabolism; Inhibitory Postsynaptic Potentials/physiology; Neurons/*metabolism; Organ Culture Techniques; Patch-Clamp Techniques; Receptors; Synapses/*metabolism; Synaptic Transmission/*physiology
Neurons of the avian cochlear nucleus magnocellularis (NM) receive glutamatergic inputs from the spiral ganglion cells via the auditory nerve and feedback GABAergic inputs primarily from the superior olivary nucleus. We investigated regulation of Ca(2+) signaling in NM neurons with ratiometric Ca(2+) imaging in chicken brain slices. Application of exogenous glutamate or GABA increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) in NM neurons. Interestingly,
Wang Lie-Cheng; Tang Zheng-Quan; Lu Yong
Neuroscience research
2012
2012-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neures.2011.11.004" target="_blank" rel="noreferrer noopener">10.1016/j.neures.2011.11.004</a>