Ectodomain shedding of nectin-1 regulates the maintenance of dendritic spine density
Article first published online: 16 DEC 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 120, Issue 5, pages 741–751, March 2012
How to Cite
Lim, S. T., Chang, A., Giuliano, R. E. and Federoff, H. J. (2012), Ectodomain shedding of nectin-1 regulates the maintenance of dendritic spine density. Journal of Neurochemistry, 120: 741–751. doi: 10.1111/j.1471-4159.2011.07592.x
- Issue published online: 10 FEB 2012
- Article first published online: 16 DEC 2011
- Accepted manuscript online: 25 NOV 2011 01:25PM EST
- Received June 23, 2011; revised manuscript received November 8, 2011; accepted November 15, 2011.
- dendritic spines;
- ectodomain shedding;
J. Neurochem. (2012) 120, 741–751.
Synaptic remodeling has been postulated as a mechanism underlying synaptic plasticity and cell adhesion molecules are thought to contribute to this process. We examined the role of nectin-1 ectodomain shedding on synaptogenesis in cultured rat hippocampal neurons. Nectins are Ca2+-independent immunoglobulin-like adhesion molecules, involved in cell-cell adherens junctions. Herein, we show that the processing of nectin-1 occurs by multiple endoproteolytic steps both in vivo and in vitro. We identified regions containing two distinct cleavage sites within the ectodomain of nectin-1. By alanine scanning mutagenesis, two point mutations that disrupt nectin-1 ectodomain cleavage events were identified. Expression of these mutants significantly alters the density of dendritic spines. These findings suggest that ectodomain shedding of nectin-1 regulates dendritic spine density and related synaptic functions.