Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R.

Nature communications 2021 Dec 08

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The brain extracellular matrix (ECM) consists of extremely long-lived proteins that assemble around neurons and synapses, to stabilize them. The ECM is thought to change only rarely, in relation to neuronal plasticity, through ECM proteolysis and renewed protein synthesis. We report here an alternative ECM remodeling mechanism, based on the recycling of ECM molecules. Using multiple ECM labeling and imaging assays, from super-resolution optical imaging to nanoscale secondary ion mass spectrometry, both in culture and in brain slices, we find that a key ECM protein, Tenascin-R, is frequently endocytosed, and later resurfaces, preferentially near synapses. The TNR molecules complete this cycle within ~3 days, in an activity-dependent fashion. Interfering with the recycling process perturbs severely neuronal function, strongly reducing synaptic vesicle exo- and endocytosis. We conclude that the neuronal ECM can be remodeled frequently through mechanisms that involve endocytosis and recycling of ECM proteins. © 2021. The Author(s).

Citation

Tal M Dankovich, Rahul Kaushik, Linda H M Olsthoorn, Gabriel Cassinelli Petersen, Philipp Emanuel Giro, Verena Kluever, Paola Agüi-Gonzalez, Katharina Grewe, Guobin Bao, Sabine Beuermann, Hannah Abdul Hadi, Jose Doeren, Simon Klöppner, Benjamin H Cooper, Alexander Dityatev, Silvio O Rizzoli. Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R. Nature communications. 2021 Dec 08;12(1):7129