2007年8月
Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage
JOURNAL OF CELL BIOLOGY
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 178
- 号
- 4
- 開始ページ
- 687
- 終了ページ
- 700
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1083/jcb.200612097
- 出版者・発行元
- ROCKEFELLER UNIV PRESS
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-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.
- リンク情報
- ID情報
-
- DOI : 10.1083/jcb.200612097
- ISSN : 0021-9525
- PubMed ID : 17682049
- Web of Science ID : WOS:000248803600014