Journal article
Spatiotemporal restriction of endothelial cell calcium signaling is required during leukocyte transmigration
The Journal of experimental medicine, Vol.218(1), e20192378
01/04/2021
DOI: 10.1084/jem.20192378
PMCID: PMC7953625
PMID: 32970800
Abstract
Endothelial cell calcium flux is critical for leukocyte transendothelial migration (TEM), which in turn is essential for the inflammatory response. Intravital microscopy of endothelial cell calcium dynamics reveals that calcium increases locally and transiently around the transmigration pore during TEM. Endothelial calmodulin (CaM), a key calcium signaling protein, interacts with the IQ domain of IQGAP1, which is localized to endothelial junctions and is required for TEM. In the presence of calcium, CaM binds endothelial calcium/calmodulin kinase IIδ (CaMKIIδ). Disrupting the function of CaM or CaMKII with small-molecule inhibitors, expression of a CaMKII inhibitory peptide, or expression of dominant negative CaMKIIδ significantly reduces TEM by interfering with the delivery of the lateral border recycling compartment (LBRC) to the site of TEM. Endothelial CaMKII is also required for TEM in vivo as shown in two independent mouse models. These findings highlight novel roles for endothelial CaM and CaMKIIδ in transducing the spatiotemporally restricted calcium signaling required for TEM.
Details
- Title: Subtitle
- Spatiotemporal restriction of endothelial cell calcium signaling is required during leukocyte transmigration
- Creators
- Prarthana J. Dalal - Northwestern UniversityDavid P. Sullivan - Northwestern UniversityEvan W. Weber - Northwestern UniversityDavid B. Sacks - National Institutes of HealthMatthias Gunzer - University of Duisburg-EssenIsabella M. Grumbach - University of IowaJoan Heller Brown - University of California San DiegoWilliam A. Muller - Northwestern University
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.218(1), e20192378
- DOI
- 10.1084/jem.20192378
- PMID
- 32970800
- PMCID
- PMC7953625
- NLM abbreviation
- J Exp Med
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL046849, HL064774; DOI: 10.13039/100005332, name: Alpha Omega Alpha Honor Medical Society; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL108932; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01HL145459; DOI: 10.13039/100000002, name: National Institutes of Health, award: T32GM8152, F30HL134202
- Language
- English
- Date published
- 01/04/2021
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984360045202771
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