TY  - JOUR
AU  - Dankovich, Tal M
AU  - Kaushik, Rahul
AU  - Olsthoorn, Linda H M
AU  - Petersen, Gabriel Cassinelli
AU  - Giro, Philipp Emanuel
AU  - Kluever, Verena
AU  - Agüi-Gonzalez, Paola
AU  - Grewe, Katharina
AU  - Bao, Guobin
AU  - Beuermann, Sabine
AU  - Hadi, Hannah Abdul
AU  - Doeren, Jose
AU  - Klöppner, Simon
AU  - Cooper, Benjamin H
AU  - Dityatev, Alexander
AU  - Rizzoli, Silvio O
TI  - Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R.
JO  - Nature Communications
VL  - 12
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2022-00371
SP  - 7129
PY  - 2021
AB  - 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.
KW  - Animals
KW  - Brain: metabolism
KW  - Endocytosis
KW  - Epitopes
KW  - Extracellular Matrix: metabolism
KW  - Extracellular Matrix Proteins: metabolism
KW  - Golgi Apparatus
KW  - Male
KW  - Membrane Transport Proteins: metabolism
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Neuronal Plasticity: physiology
KW  - Neurons: metabolism
KW  - Synapses: metabolism
KW  - Tenascin: metabolism
KW  - Epitopes (NLM Chemicals)
KW  - Extracellular Matrix Proteins (NLM Chemicals)
KW  - Membrane Transport Proteins (NLM Chemicals)
KW  - Tenascin (NLM Chemicals)
KW  - tenascin R (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34880248
C2  - pmc:PMC8654841
DO  - DOI:10.1038/s41467-021-27462-7
UR  - https://pub.dzne.de/record/163625
ER  -