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Interpericyte tunnelling nanotubes regulate neurovascular coupling

Alarcon-Martinez, Luis, Villafranca-Baughman, Deborah, Quintero, Heberto, Kacerovsky, J. Benjamin, Dotigny, Florence, Murai, Keith K., Prat, Alexandre, Drapeau, Pierre, Di Polo, Adriana·2020·Nature
DOI 10.1038/s41586-020-2589-x
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Abstract

Signalling between cells of the neurovascular unit, or neurovascular coupling, is essential to match local blood flow with neuronal activity. Pericytes interact with endothelial cells and extend processes that wrap capillaries, covering up to 90% of their surface area 1,2 . Pericytes are candidates to regulate microcirculatory blood flow because they are strategically positioned along capillaries, contain contractile proteins and respond rapidly to neuronal stimulation 3,4 , but whether they synchronize microvascular dynamics and neurovascular coupling within a capillary network was unknown. Here we identify nanotube-like processes that connect two bona fide pericytes on separate capillary systems, forming a functional network in the mouse retina, which we named interpericyte tunnelling nanotubes (IP-TNTs). We provide evidence that these (i) have an open-ended proximal side and a closed-ended terminal (end-foot) that connects with distal pericyte processes via gap junctions, (ii) carry organelles including mitochondria, which can travel along these processes, and (iii) serve as a conduit for intercellular Ca 2+ waves, thus mediating communication between pericytes. Using two-photon microscope live imaging, we demonstrate that retinal pericytes rely on IP-TNTs to control local neurovascular coupling and coordinate light-evoked responses between adjacent capillaries. IP-TNT damage following ablation or ischaemia disrupts intercellular Ca 2+ waves, impairing blood flow regulatio…

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Research works printed but not linked: 28

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Metadata

Authors
Alarcon-Martinez, L., Villafranca-Baughman, D., Quintero, H., Kacerovsky, J. B., Dotigny, F., Murai, K. K., Prat, A., Drapeau, P., & Di Polo, A.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2020-08-12
Volume
585
Issue
7823
Pages
91-95
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/s41586-020-2589-x
Cited by
312
References
2
Language
en
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