Interaction between MyRIP and the actin cytoskeleton regulates Weibel-Palade body trafficking and exocytosis
More about Open Access at the CrickAuthors list
Ianina L Conte Nicola Hellen Ruben Bierings Gregory Mashanov Jean-Baptiste Manneville Nikolai I Kiskin Matthew J Hannah Justin Molloy Tom CarterAbstract
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 Ca(2+)-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 Ca(2+)-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.
Journal details
Journal Journal of Cell Science
Volume 129
Issue number 3
Pages 592-603
Available online
Publication date
Full text links
Publisher website (DOI) 10.1242/jcs.178285
Figshare View on figshare
Europe PubMed Central 26675235
Pubmed 26675235
Keywords
Related topics
Type of publication