Open AccessTransient ECM protease activity promotes synaptic plasticity
Author(s) -
Marta Magnowska,
Tomasz Górkiewicz,
Anna Suska,
Marcin Wawrzyniak,
Izabela Rutkowska-Włodarczyk,
Leszek Kaczmarek,
Jakub Włodarczyk
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27757
Subject(s) - long term potentiation , dendritic spine , synaptic plasticity , ampa receptor , synapse , microbiology and biotechnology , protease , nmda receptor , proteolysis , glutamate receptor , biology , chemistry , neuroscience , receptor , biochemistry , enzyme , hippocampal formation
Activity-dependent proteolysis at a synapse has been recognized as a pivotal factor in controlling dynamic changes in dendritic spine shape and function; however, excessive proteolytic activity is detrimental to the cells. The exact mechanism of control of these seemingly contradictory outcomes of protease activity remains unknown. Here, we reveal that dendritic spine maturation is strictly controlled by the proteolytic activity, and its inhibition by the endogenous inhibitor (Tissue inhibitor of matrix metalloproteinases-1 – TIMP-1). Excessive proteolytic activity impairs long-term potentiation of the synaptic efficacy (LTP), and this impairment could be rescued by inhibition of protease activity. Moreover LTP is altered persistently when the ability of TIMP-1 to inhibit protease activity is abrogated, further demonstrating the role of such inhibition in the promotion of synaptic plasticity under well-defined conditions. We also show that dendritic spine maturation involves an intermediate formation of elongated spines, followed by their conversion into mushroom shape. The formation of mushroom-shaped spines is accompanied by increase in AMPA/NMDA ratio of glutamate receptors. Altogether, our results identify inhibition of protease activity as a critical regulatory mechanism for dendritic spines maturation.