Translational regulation of matrix metalloproteinase 9 mRNA at the synapse

• Autorzy: Dziiembowska M. , Milek J. , Jasinska M. , Leski S. , Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Matrix metalloproteinase 9 (MMP-9) is locally translated in dendrites in response to synaptic stimulation. Its enzymatic activity at the synapse is involved in the reorganization of spine architecture and was shown to regulate spine morphology in Fragile X syndrome (FXS) which is caused by the loss of mental retardation protein (FMRP). Application of MMP-9 on neurons in culture induces formation of filopodia-like immature dendritic spines that resembles these in FXS. Furthermore, inhibiting MMP-9 activity by application of minocycline, the tetracycline analogue, to Fmr1 KO mice can rescue the abnormal spine phenotype both in vivo and in cultured neurons. Deregulation of local protein synthesis at the synapse contributes to spine dysmorphogenesis and synaptic dysfunction in patients with the Fragile X Syndrome. RESULTS: Here we show that MMP-9 mRNA is a specific target of FMRP and that FMRP regulates its transport and translation at the synapse. In the absence of FMRP MMP-9 mRNA translation is increased and this causes an excess of active MMP-9 protein at synapses leading to the abnormal spine morphology. Moreover our results indicate that synaptic translation of MMP-9 can be regulated by microRNAs. CONCLUSIONS: Our data support a model in which synaptic MMP-9 mRNA is translationally regulated by FMRP and microRNAs. We propose that the regulation of synaptic MMP-9 mRNA translation can contribute to the aberrant spine morphology observed in patients with FXS.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S65-S66

Twórcy

autor

Dziiembowska M.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
• Laboratory of Molecular Basis of Synaptic Plasticity, Center of New Technologies, Warsaw University, Warsaw, Poland

autor

Milek J.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
• Laboratory of Molecular Basis of Synaptic Plasticity, Center of New Technologies, Warsaw University, Warsaw, Poland

autor

Jasinska M.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
• Laboratory of Molecular Basis of Synaptic Plasticity, Center of New Technologies, Warsaw University, Warsaw, Poland

autor

Leski S.

• Laboratory of Neuroinformatics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Kaczmarek L.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland