A junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis
Tsveta S. Malinova,
Ana Angulo-Urarte,
Julian Nüchel,
Marina Tauber,
Miesje M. van der Stoel,
Vera Janssen,
Annett de Haan,
Anouk G. Groenen,
Merel Tebbens,
Mariona Graupera,
Markus Plomann and
Stephan Huveneers ()
Additional contact information
Tsveta S. Malinova: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Ana Angulo-Urarte: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Julian Nüchel: University of Cologne
Marina Tauber: University of Cologne
Miesje M. van der Stoel: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Vera Janssen: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Annett de Haan: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Anouk G. Groenen: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Merel Tebbens: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Mariona Graupera: Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l’Hospitalet 199, 08908 L’Hospitalet de Llobregat
Markus Plomann: University of Cologne
Stephan Huveneers: Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, location AMC
Nature Communications, 2021, vol. 12, issue 1, 1-18
Abstract:
Abstract Angiogenic sprouting relies on collective migration and coordinated rearrangements of endothelial leader and follower cells. VE-cadherin-based adherens junctions have emerged as key cell-cell contacts that transmit forces between cells and trigger signals during collective cell migration in angiogenesis. However, the underlying molecular mechanisms that govern these processes and their functional importance for vascular development still remain unknown. We previously showed that the F-BAR protein PACSIN2 is recruited to tensile asymmetric adherens junctions between leader and follower cells. Here we report that PACSIN2 mediates the formation of endothelial sprouts during angiogenesis by coordinating collective migration. We show that PACSIN2 recruits the trafficking regulators EHD4 and MICAL-L1 to the rear end of asymmetric adherens junctions to form a recycling endosome-like tubular structure. The junctional PACSIN2/EHD4/MICAL-L1 complex controls local VE-cadherin trafficking and thereby coordinates polarized endothelial migration and angiogenesis. Our findings reveal a molecular event at force-dependent asymmetric adherens junctions that occurs during the tug-of-war between endothelial leader and follower cells, and allows for junction-based guidance during collective migration in angiogenesis.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22873-y
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DOI: 10.1038/s41467-021-22873-y
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