Journal Article

DZNE-2022-00371

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R.

Dankovich, T. M. ; Kaushik, R.DZNE* ; Olsthoorn, L. H. M. ; Petersen, G. C. ; Giro, P. E. ; Kluever, V. ; Agüi-Gonzalez, P. ; Grewe, K. ; Bao, G. ; Beuermann, S. ; Hadi, H. A. ; Doeren, J. ; Klöppner, S. ; Cooper, B. H. ; Dityatev, A.DZNE* ; Rizzoli, S. O.

2021
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-021-27462-7

Abstract: 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.

Keyword(s): Animals (MeSH) ; Brain: metabolism (MeSH) ; Endocytosis (MeSH) ; Epitopes (MeSH) ; Extracellular Matrix: metabolism (MeSH) ; Extracellular Matrix Proteins: metabolism (MeSH) ; Golgi Apparatus (MeSH) ; Male (MeSH) ; Membrane Transport Proteins: metabolism (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Neuronal Plasticity: physiology (MeSH) ; Neurons: metabolism (MeSH) ; Synapses: metabolism (MeSH) ; Tenascin: metabolism (MeSH) ; Epitopes ; Extracellular Matrix Proteins ; Membrane Transport Proteins ; Tenascin ; tenascin R

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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