Interaction between MyRIP and the actin cytoskeleton regulates Weibel-Palade body trafficking and exocytosis
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Published version
Author(s)
Type
Journal Article
Abstract
Weibel–Palade body (WPB)–actin interactions are essential for the trafficking and secretion of von Willebrand factor; however, the molecular basis for this interaction remains poorly defined. Myosin Va (MyoVa or MYO5A) is recruited to WPBs by a Rab27A–MyRIP complex and is thought to be the prime mediator of actin binding, but direct MyRIP–actin interactions can also occur. To evaluate the specific contribution of MyRIP–actin and MyRIP–MyoVa binding in WPB trafficking and Ca2+-driven exocytosis, we used EGFP–MyRIP point mutants with disrupted MyoVa and/or actin binding and high-speed live-cell fluorescence microscopy. We now show that the ability of MyRIP to restrict WPB movement depends upon its actin-binding rather than its MyoVa-binding properties. We also show that, although the role of MyRIP in Ca2+-driven exocytosis requires both MyoVa- and actin-binding potential, it is the latter that plays a dominant role. In view of these results and together with the analysis of actin disruption or stabilisation experiments, we propose that the role of MyRIP in regulating WPB trafficking and exocytosis is mediated largely through its interaction with actin rather than with MyoVa.
Date Issued
2016-02-01
Date Acceptance
2015-12-03
ISSN
0021-9533
Publisher
Company of Biologists
Start Page
592
End Page
603
Journal / Book Title
Journal of Cell Science
Volume
129
Issue
3
Copyright Statement
© 2016. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Identifier
https://jcs.biologists.org/content/129/3/592
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Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Actin
Exocytosis
MyRIP
Myosin Va
Weibel-Palade body
VON-WILLEBRAND-FACTOR
HUMAN ENDOTHELIAL-CELLS
MYOSIN VA RECRUITMENT
PROTEIN-KINASE-A
SECRETORY GRANULES
PLASMA-MEMBRANE
MELANOSOME TRANSPORT
TEMPORAL DYNAMICS
SINGLE MOLECULES
BINDING DOMAIN
Actin
Exocytosis
MyRIP
Myosin Va
Weibel–Palade body
Actin Cytoskeleton
Actins
Calcium
Cell Line
Cell Movement
Exocytosis
Green Fluorescent Proteins
Human Umbilical Vein Endothelial Cells
Humans
Myosin Heavy Chains
Myosin Type V
Protein Binding
Protein Transport
Vesicular Transport Proteins
Weibel-Palade Bodies
Cell Line
Weibel-Palade Bodies
Humans
Calcium
Actins
Myosin Type V
Myosin Heavy Chains
Green Fluorescent Proteins
Vesicular Transport Proteins
Cell Movement
Exocytosis
Protein Binding
Protein Transport
Actin Cytoskeleton
Human Umbilical Vein Endothelial Cells
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Actin
Exocytosis
MyRIP
Myosin Va
Weibel-Palade body
VON-WILLEBRAND-FACTOR
HUMAN ENDOTHELIAL-CELLS
MYOSIN VA RECRUITMENT
PROTEIN-KINASE-A
SECRETORY GRANULES
PLASMA-MEMBRANE
MELANOSOME TRANSPORT
TEMPORAL DYNAMICS
SINGLE MOLECULES
BINDING DOMAIN
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status
Published
Date Publish Online
2016-02-01