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The small GTPase Ra...
The small GTPase Rab5c is a key regulator of trafficking of the CD93/Multimerin-2/1 integrin complex in endothelial cell adhesion and migration
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- Barbera, Stefano (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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- Nardi, Federica (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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- Elia, Ines (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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- Realini, Giulia (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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- Lugano, Roberta (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi
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- Santucci, Annalisa (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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- Tosi, Gian Marco (author)
- Univ Siena, Dept Med Surg & Neurosci, Ophthalmol Unit, Policlin Le Scotte, Viale Bracci, I-53100 Siena, Italy
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- Dimberg, Anna (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Galvagni, Federico (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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- Orlandini, Maurizio (author)
- Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro 2, I-53100 Siena, Italy
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(creator_code:org_t)
- 2019-05-28
- 2019
- English.
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In: Cell Communication and Signaling. - : Springer Science and Business Media LLC. - 1478-811X. ; 17
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Abstract
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- BackgroundIn the endothelium, the single-pass membrane protein CD93, through its interaction with the extracellular matrix protein Multimerin-2, activates signaling pathways that are critical for vascular development and angiogenesis. Trafficking of adhesion molecules through endosomal compartments modulates their signaling output. However, the mechanistic basis coordinating CD93 recycling and its implications for endothelial cell (EC) function remain elusive.MethodsHuman umbilical vein ECs (HUVECs) and human dermal blood ECs (HDBEC) were used in this study. Fluorescence confocal microscopy was employed to follow CD93 retrieval, recycling, and protein colocalization in spreading cells. To better define CD93 trafficking, drug treatments and transfected chimeric wild type and mutant CD93 proteins were used. The scratch assay was used to evaluate cell migration. Gene silencing strategies, flow citometry, and quantification of migratory capability were used to determine the role of Rab5c during CD93 recycling to the cell surface.ResultsHere, we identify the recycling pathway of CD93 following EC adhesion and migration. We show that the cytoplasmic domain of CD93, by its interaction with Moesin and F-actin, is instrumental for CD93 retrieval in adhering and migrating cells and that aberrant endosomal trafficking of CD93 prevents its localization at the leading edge of migration. Moreover, the small GTPase Rab5c turns out to be a key component of the molecular machinery that is able to drive CD93 recycling to the EC surface. Finally, in the Rab5c endosomal compartment CD93 forms a complex with Multimerin-2 and active 1 integrin, which is recycled back to the basolaterally-polarized cell surface by clathrin-independent endocytosis.ConclusionsOur findings, focusing on the pro-angiogenic receptor CD93, unveil the mechanisms of its polarized trafficking during EC adhesion and migration, opening novel therapeutic opportunities for angiogenic diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- Cell polarity
- Cell spreading
- Moesin
- C1qRp
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Barbera, Stefano
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Nardi, Federica
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Elia, Ines
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Realini, Giulia
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Lugano, Roberta
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Santucci, Annali ...
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Tosi, Gian Marco
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Dimberg, Anna
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Galvagni, Federi ...
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Orlandini, Mauri ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Cell Communicati ...
- By the university
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Uppsala University