Activity - dependent cleavage of Nectin-3 is mediated by MMP-9 metalloproteinase

• Autorzy: Rejmak E. , Kalita-Bykowska K. , Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

Matrix metalloproteinase-9 regulates pericellular environment through cleavage of protein components of the extracellular matrix as well as cell adhesion molecules. Recently, it has been revealed that MMP-9 plays an important role in the synaptic plasticity. However, only one synaptic target for its enzymatic activity, beta-dystroglycan was identified to date. In this report we show that Nectin-3 the Ca2+- independent immunoglobulin-like cell adhesion molecule, is a potential substrate for MMP-9. We found that NMDA receptor activation resulted in robust ectodomain shedding of Nectin-3 in the hippocampal cultures. The effect was abolished in the presence of NMDA receptor antagonists, APV and MK801. In contrast, pretreatment with either nifedipine or CNQX only partially decreased NMDA-induced Nectin-3 shedding. Using EGTA, the calcium chelator, we showed that NMDA-mediated cleavage of Nectin-3 was calcium dependent. In addition, we observed Nectin-3 cleavage in the presence of calcium ionophore ionomycin. To test if MMP-9 is mediating Nectin-3 shedding we pretreated hippocampal neurons with inhibitor of MMP-9 and found that this tretment completely abolishes Nectin-3 cleavage evoked by wither NMDA or ionomycin. Our results suggest that ecodomain shedding of Nectin-3 is Ca2+-regulated event and MMP-9 can potentially be responsible for these cleavages.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: S
• Opis fizyczny: p.46

Twórcy

autor

Rejmak E.

• Department of Molecular Neurobiology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland

autor

Kalita-Bykowska K.

• Department of Molecular Neurobiology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland

autor

Kaczmarek L.

• Department of Molecular Neurobiology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland

Uwagi

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