eISSN: 2084-9885
ISSN: 1896-6764
Neuropsychiatria i Neuropsychologia/Neuropsychiatry and Neuropsychology
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vol. 3

Proteomics of proteases in the example of the possible role of MMP-9 in synaptic plasticity

Piotr Michaluk
Marcin Rylski
Leszek Kaczmarek

Neuropsychiatria i Neuropsychologia 2008; 3, 3–4: 95–106
Online publish date: 2008/11/25
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More and more proteases are viewed as precise cellular mechanisms, which may regulate biological processes in all organisms, and not only as unspecific enzymes involved in catalysis of proteins. For this reason new experimental approaches are needed, which may explain the role of proteases and regulation of their activity on all levels of protein expression, starting from gene transcription, ending with inhibition of activity by endogenous inhibitors. In our research, we focused on finding new elements regulating transcription of the mmp-9 (matrix metalloproteinase-9) gene and on finding new substrates for this enzyme in the brain. Thanks to the footprinting method we identified YY1 factor, which turned out to be an mmp-9 gene repressor in non-stimulated and activator in stimulated neurons. Using chromatin immunoprecipitation (ChIP) and immunoprecipitation (IP) and analyzing resulting samples by mass spectrometry, we identified many potential partners binding to YY1 in vivo in non-stimulated and stimulated neurons. Studying the activity of MMP-9 protein, we have shown that cleavage of b-dystroglycan (transmembrane protein occurring on neuronal synapses) by MMP-9, released as a result of neuronal excitation, is potentially important in synaptic plasticity, a process which is probably a base of learning and memory. In a later part of this paper, we explain the new concept of “proteodegradomics” and we set together methods which are useful in finding new substrates for proteases and analysing the level of proteolysis in various states of the cell.

MMP-9, YY1, mózg, proteomika, macierz zewnątrzkomórkowa, proteazy

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