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Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage.
- Source :
-
Journal of Cell Biology . 8/13/2007, Vol. 178 Issue 4, p687-700. 14p. - Publication Year :
- 2007
-
Abstract
- Matrix metalloproteinase (MMP)-2 and -9 are pivotal in remodeling many tissues. However, their functions and candidate substrates for brain development are poorly characterized. Intercellular adhesion molecule-5 (ICAM-5; Telencephalin) is a neuronal adhesion molecule that regulates dendritic elongation and spine maturation. We find that ICAM-5 is cleaved from hippocampal neurons when the cells are treated with N-methyl-D-aspartic acid (NMDA) or α-amino-3-hydroxy5-methylisoxazole-propionic acid (AMPA). The cleavage is blocked by MMP-2 and -9 inhibitors and small interfering RNAs. Newborn MMP-2- and MMP-9-deficient mice brains contain more full-length ICAM-5 than wild-type mice. NMDA receptor activation disrupts the actin cytoskeletal association of ICAM-5, which promotes its cleavage. ICAM-5 is mainly located in dendritic filopodia and immature thin spines. MMP inhibitors block the NMDA-induced cleavage of ICAM-5 more efficiently in dendritic shafts than in thin spines. ICAM-5 deficiency causes retraction of thin spine heads in response to NMDA stimulation. Soluble ICAM-5 promotes elongation of dendritic filopodia from wild-type neurons, but not from ICAM-5-deficient neurons. Thus, MMPs are important for ICAM-5-mediated dendritic spine development. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219525
- Volume :
- 178
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 26324980
- Full Text :
- https://doi.org/10.1083/jcb.200612097