[Abstract Title]. - Society for Neuroscience

Poster
279. Steroids and Plasticity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 279.8/MM22
Topic: E.01.c. Steroids and plasticity
Support: NIH Grant NS07080
NIH Grant 5P01 AG16765
Title: PELP1 associates with PSD-95 and localizes to dendrites in hippocampal neurons
Authors: *K. T. AKAMA 1 , K. L. MITTERLING 2 , T. A. MILNER 1,2 , B. S. MCEWEN 1 ;
1 Neuroendocrinol, Rockefeller Univ., New York, NY; 2 Neurol. and Neurosci., Weill Cornell
Med. Col., New York, NY
Abstract: Dendritic spines are often the sites of excitatory synapse formation, and the steroid
hormone estrogen stimulates an increase in spine formation and subsequent synaptogenesis in the
hippocampus. Recent studies have demonstrated that the estrogen receptors (ER) can be
immuno-localized to non-nuclear sites in hippocampal CA1 pyramidal cell dendrites, particularly
spines. Such spine-targeting of ER‟s potentially allows for local signaling from hormonal stimuli
to rapidly modify dendritic spine structure or downstream neuronal responses. Our objective is to
identify specific protein binding partners that might selectively direct a rapid, estrogenstimulated
non-genomic response, and therefore we are investigating the molecular interactions
of ER‟s with spine proteins. A key protein that we are addressing here is the ER scaffolding
protein, PELP1 (proline-, glutamic acid-, leucine-rich protein 1). ERα is known to associate with
PELP1 (also known as MNAR, modulator of non-genomic activity of ER), and an ERα-PELP1
interaction can result in estrogen-stimulated Src kinase signal transduction in breast cancer cells.
Consistent with previous studies, PELP1 immuno-reactivity was detected in the nuclei of
hippocampal pyramidal cells. Additionally, electron microscopic studies revealed PELP1
immuno-reactivity in dendritic shafts and spines in CA1 stratum radiatum. Likewise, such
PELP1 localization might be facilitated via the spine scaffolding protein PSD-95 (post-synaptic
density protein-95). We further demonstrate here in vitro by co-immunoprecipitation assays that
PELP1 protein associates with PSD-95. Thus, these findings suggest that certain non-genomic
estrogen actions at the dendritic spine may occur via the cellular localization and the molecular
function of PELP1.
Disclosures: K.T. Akama, None; B.S. McEwen, None; T.A. Milner, None; K.L. Mitterling,
None.