| First Author | Tian L | Year | 2007 |
| Journal | J Cell Biol | Volume | 178 |
| Issue | 4 | Pages | 687-700 |
| PubMed ID | 17682049 | Mgi Jnum | J:150623 |
| Mgi Id | MGI:3851082 | Doi | 10.1083/jcb.200612097 |
| Citation | Tian L, et al. (2007) Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage. J Cell Biol 178(4):687-700 |
| abstractText | 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 alpha-amino-3-hydroxy-5-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. |
