Myosin-1C augments endothelial secretion of von Willebrand factor by linking contractile actomyosin machinery to the plasma membrane
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Blood endothelial cells control the hemostatic and inflammatory response by secreting von Willebrand factor (VWF) and P-selectin from storage organelles called Weibel-Palade bodies (WPBs). Actin-associated motor proteins regulate this secretory pathway at multiple points. Before fusion, myosin Va forms a complex that anchors WPBs to peripheral actin structures, allowing for the maturation of content. After fusion, an actomyosin ring/coat is recruited and compresses the WPB to forcibly expel the largest VWF multimers. Here, we provide, to our knowledge, the first evidence for the involvement of class I myosins during regulated VWF secretion. We show that the unconventional myosin-1C (Myo1c) is recruited after fusion via its pleckstrin homology domain in an actin-independent process. This provides a link between the actin ring and phosphatidylinositol 4,5-bisphosphate (PIP2) at the membrane of the fused organelle and is necessary to ensure maximal VWF secretion. This is an active process requiring Myo1c ATPase activity because inhibition of class I myosins using the inhibitor pentachloropseudilin or expression of an ATPase-deficient Myo1c rigor mutant perturbs the expulsion of VWF and alters the kinetics of the exocytic actin ring. These data offer a novel insight into the control of an essential physiological process and provide a new way in which it can be regulated.
Date Issued
2024-09-10
Date Acceptance
2024-04-16
Citation
Blood Advances, 2024, 8 (17), pp.4714-4726
ISSN
2473-9537
Publisher
American Society of Hematology (ASH Publications)
Start Page
4714
End Page
4726
Journal / Book Title
Blood Advances
Volume
8
Issue
17
Copyright Statement
© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38669344
PII: 515905
Subjects
ACTIN
EXOCYTOSIS
Hematology
INSULIN
Life Sciences & Biomedicine
MYO1C
MYRIP
PROMOTES
PROTEIN
Science & Technology
TRAFFICKING
VONWILLEBRAND-FACTOR
WEIBEL-PALADE BODIES
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-04-26