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Proteomika proteaz na przykładzie możliwej roli MMP-9 w plastyczności synaptycznej*

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Author(s): Piotr Michaluk | Marcin Rylski | Leszek Kaczmarek

Journal: Neuropsychiatria i Neuropsychologia
ISSN 1896-6764

Volume: 3;
Issue: 3-4;
Start page: 95;
Date: 2008;
Original page

Keywords: MMP-9 | YY1 | brain | proteomics | extracellular matrix | proteases

ABSTRACT
More and more proteases are viewed as precise cellularmechanisms, which may regulate biological processesin all organisms, and not only as unspecific enzymesinvolved in catalysis of proteins. For this reason newexperimental approaches are needed, which mayexplain the role of proteases and regulation of theiractivity on all levels of protein expression, starting fromgene transcription, ending with inhibition of activityby endogenous inhibitors. In our research, we focusedon finding new elements regulating transcription ofthe mmp-9 (matrix metalloproteinase-9) gene and onfinding new substrates for this enzyme in the brain.Thanks to the footprinting method we identified YY1factor, which turned out to be an mmp-9 gene repressorin non-stimulated and activator in stimulated neurons.Using chromatin immunoprecipitation (ChIP) andimmunoprecipitation (IP) and analyzing resultingsamples by mass spectrometry, we identified manypotential partners binding to YY1 in vivo in nonstimulatedand stimulated neurons. Studying theactivity of MMP-9 protein, we have shown thatcleavage of β-dystroglycan (transmembrane proteinoccurring on neuronal synapses) by MMP-9, releasedas a result of neuronal excitation, is potentiallyimportant in synaptic plasticity, a process which isprobably a base of learning and memory. In a later partof this paper, we explain the new concept of“proteodegradomics” and we set together methodswhich are useful in finding new substrates for proteasesand analysing the level of proteolysis in various statesof the cell.

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