Dendritic spines are numerous small membrane appendages on the surface of dendrites. Mature dendritic spines, which typically show either a mushroom-like or stub-like shape, develop from thin, filopodia-like protrusions. This morphological maturation of spines occurs during development and the process of learning, while abnormal spines have been demonstrated in patients with mental retardation and autism. We have recently found that the cell surface heparan sulfate proteoglycan syndecan-2 plays a functional role in the development of dendritic spines. Syndecan-2 becomes concentrated in dendritic spines concomitant with their morphological maturation. More importantly, transfection of syndecan-2 induces the formation of mature spines in young neurons which normally do not contain mature spines. Deletion studies have indicated that the C-terminal EFYA motif is required for the spine- inducing activity of syndecan-2, whereas the clustering of syndecan-2, which is a process preceding spine maturation, requires the rest of the syndecan-2 cytoplasmic domain. This project is aimed at elucidating the molecular interactions and signaling events involving the syndecan-2 cytoplasmic domain, leading to improved understanding of the mechanism of dendritic spine development. Toward this goal, we will: 1. Investigate the role of phosphorylation of the syndecan-2 cytoplasmic domain in syndecan-2 clustering in dendritic spines and their morphological maturation. 2. Identify neuronal molecules interacting with the C1 and V regions of the syndecan-2 cytoplasmic domain. 3. Determine the role of Rho family GTPase in syndecan-2 induce spine maturation. 4. Characterize P24syn2, a novel protein that binds to the EFYA tail of syndecan-2, in comparison with other known EFYA-binding proteins, CASK and syntenin, and identify physiological relevant EFYA-binding proteins involved in syndecan-2 induced spine maturation.

Project Start
2000-05-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
11
Fiscal Year
2000
Total Cost
$200,480
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Yotsumoto, Fusanori; You, Weon-Kyoo; Cejudo-Martin, Pilar et al. (2015) NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte-endothelial cell interactions required for brain tumor vascularization. Oncoimmunology 4:e1001204
Arranz, Amaia M; Perkins, Katherine L; Irie, Fumitoshi et al. (2014) Hyaluronan deficiency due to Has3 knock-out causes altered neuronal activity and seizures via reduction in brain extracellular space. J Neurosci 34:6164-76
Vargas, Lina M; Leal, Nancy; Estrada, Lisbell D et al. (2014) EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-? oligomers. PLoS One 9:e92309
You, Weon-Kyoo; Yotsumoto, Fusanori; Sakimura, Kenji et al. (2014) NG2 proteoglycan promotes tumor vascularization via integrin-dependent effects on pericyte function. Angiogenesis 17:61-76
Cattaruzza, Sabrina; Ozerdem, Ugur; Denzel, Martin et al. (2013) Multivalent proteoglycan modulation of FGF mitogenic responses in perivascular cells. Angiogenesis 16:309-27
Tigges, Ulrich; Komatsu, Masanobu; Stallcup, William B (2013) Adventitial pericyte progenitor/mesenchymal stem cells participate in the restenotic response to arterial injury. J Vasc Res 50:134-44
Falivelli, Giulia; Lisabeth, Erika Mathes; Rubio de la Torre, Elena et al. (2013) Attenuation of eph receptor kinase activation in cancer cells by coexpressed ephrin ligands. PLoS One 8:e81445
Noberini, Roberta; Koolpe, Mitchell; Lamberto, Ilaria et al. (2012) Inhibition of Eph receptor-ephrin ligand interaction by tea polyphenols. Pharmacol Res 66:363-73
Gibby, Krissa; You, Weon-Kyoo; Kadoya, Kuniko et al. (2012) Early vascular deficits are correlated with delayed mammary tumorigenesis in the MMTV-PyMT transgenic mouse following genetic ablation of the NG2 proteoglycan. Breast Cancer Res 14:R67
Noberini, Roberta; Rubio de la Torre, Elena; Pasquale, Elena B (2012) Profiling Eph receptor expression in cells and tissues: a targeted mass spectrometry approach. Cell Adh Migr 6:102-12

Showing the most recent 10 out of 118 publications