Skip to main content
  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

  • Home
  • About this Journal
    • Editorial Board
    • Meet the Editors
    • ATVB Journal History
    • General Statistics
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • Cover Art Award
    • ATVB Early Career Award
    • ATVB in Focus
    • Recent Brief Reviews of ATVB
    • Lecture Series
    • Collections
    • Recent Highlights of ATVB
    • Commentaries
    • Browse Abstracts
    • Insight into ATVB Authors
  • Resources
    • Instructions for Authors
    • Online Submission/Peer Review Site
    • Council on ATVB
    • Permissions and Rights Q&A
    • AHA Guidelines and Statements
    • Customer Service and Ordering Information
    • Author Reprints
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
  • Facebook
  • LinkedIn
  • Twitter

  • My alerts
  • Sign In
  • Join

  • Advanced search

Header Publisher Menu

  • American Heart Association
  • Science Volunteer
  • Warning Signs
  • Advanced Search
  • Donate

Arteriosclerosis, Thrombosis, and Vascular Biology

  • My alerts
  • Sign In
  • Join

  • Facebook
  • LinkedIn
  • Twitter
  • Home
  • About this Journal
    • Editorial Board
    • Meet the Editors
    • ATVB Journal History
    • General Statistics
  • All Issues
  • Subjects
    • All Subjects
    • Arrhythmia and Electrophysiology
    • Basic, Translational, and Clinical Research
    • Critical Care and Resuscitation
    • Epidemiology, Lifestyle, and Prevention
    • Genetics
    • Heart Failure and Cardiac Disease
    • Hypertension
    • Imaging and Diagnostic Testing
    • Intervention, Surgery, Transplantation
    • Quality and Outcomes
    • Stroke
    • Vascular Disease
  • Browse Features
    • Cover Art Award
    • ATVB Early Career Award
    • ATVB in Focus
    • Recent Brief Reviews of ATVB
    • Lecture Series
    • Collections
    • Recent Highlights of ATVB
    • Commentaries
    • Browse Abstracts
    • Insight into ATVB Authors
  • Resources
    • Instructions for Authors
    • Online Submission/Peer Review Site
    • Council on ATVB
    • Permissions and Rights Q&A
    • AHA Guidelines and Statements
    • Customer Service and Ordering Information
    • Author Reprints
    • International Users
    • AHA Newsroom
  • AHA Journals
    • AHA Journals Home
    • Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB)
    • Circulation
    • → Circ: Arrhythmia and Electrophysiology
    • → Circ: Genomic and Precision Medicine
    • → Circ: Cardiovascular Imaging
    • → Circ: Cardiovascular Interventions
    • → Circ: Cardiovascular Quality & Outcomes
    • → Circ: Heart Failure
    • Circulation Research
    • Hypertension
    • Stroke
    • Journal of the American Heart Association
Oral Abstract PresentationsSession Title: Plenary Session IV: Young Investigator Award Competition

Abstract 45: Characterization of a Novel Integrin Binding Protein that is Essential for αIIbβ3 Outside-in Signaling and Hemostasis

Binggang Xiang, Guoying Zhang, Shaojing Ye, Cai Huang, Jun Liu, Min Tao, Changgeng Ruan, Susan Smyth, Sidney Whiteheart, Zhenyu Li
Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;35:A45
Binggang Xiang
Div of Cardiovascular Medicine, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guoying Zhang
Div of Cardiovascular Medicine, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaojing Ye
Dept of Molecular and Cellular Biochemistry, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cai Huang
Markey Cancer Cntr, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun Liu
Dept of Biochemistry and Molecular Biology, Mayo Clinic in Arizona, Scottsdale, AZ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Min Tao
Dept of Oncology, the First Affiliated Hosp of Soochow Univ, Suzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Changgeng Ruan
Jiangsu Institute of Hematology, the First Affiliated Hosp of Soochow Univ, Suzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan Smyth
Div of Cardiovascular Medicine, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sidney Whiteheart
Dept of Molecular and Cellular Biochemistry, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhenyu Li
Div of Cardiovascular Medicine, Univ of Kentucky, Lexington, KY
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics

Jump to

  • Article
  • Info & Metrics
  • eLetters
Loading

Abstract

Integrins are heterodimeric (α/β) membrane proteins that play fundamental roles in many biological processes, e.g. cell adhesion and spreading, which are important for platelet function and hemostasis. Integrin function is modulated by bi-directional transmembrane signaling: inside-out and outside-in, which is mediated through the interactions between integrin cytoplasmic tails and intracellular, regulatory proteins. Here, we show that VPS33B, a member of the Sec1/Munc18 (SM) family and component of the Class C core of the CORVET/HOPS sorting complexes, binds directly to the β subunit. Overexpression of VPS33B in CHO cells potentiated αIIbβ3 outside-in signaling but not inside-out signaling. Platelets, from megakaryocyte- and platelet-specific VPS33B conditional knockout mice we generated, had normal morphology yet their spreading on fibrinogen was impaired and they failed to support clot retraction. Platelet aggregation and ATP secretion in response to low-dose thrombin were reduced in the VPS33B knockout mice. αIIbβ3-mediated endocytosis of fibrinogen was also defective. Tail bleeding times were prolonged in the VPS33B knockout mice. Furthermore, VPS33B acted upstream of the RhoA-ROCK-MLC and Rac1 dependent pathways that leads to clot retraction and cell spreading, respectively. Our work demonstrates that vesicular trafficking complexes are a novel class of modifiers of integrin function and in hemostasis. Our data also provide insights into the molecular mechanism and treatment of ARC syndrome.

  • Hemostasis
  • Blood cells
  • Cell signaling
  • Author Disclosures: B. Xiang: None. G. Zhang: None. S. Ye: None. C. Huang: None. J. Liu: None. M. Tao: None. C. Ruan: None. S. Smyth: None. S. Whiteheart: None. Z. Li: None.

  • This research has received full or partial funding support from the American Heart Association.

  • © 2015 by American Heart Association, Inc.
Back to top
Previous Article

This Issue

Arteriosclerosis, Thrombosis, and Vascular Biology
May 2015, Volume 35, Issue Suppl 1
  • Table of Contents
Previous Article

Jump to

  • Article
  • Info & Metrics

Article Tools

  • Citation Tools
    Abstract 45: Characterization of a Novel Integrin Binding Protein that is Essential for αIIbβ3 Outside-in Signaling and Hemostasis
    Binggang Xiang, Guoying Zhang, Shaojing Ye, Cai Huang, Jun Liu, Min Tao, Changgeng Ruan, Susan Smyth, Sidney Whiteheart and Zhenyu Li
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;35:A45, originally published August 11, 2015

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
  • Article Alerts
    Log in to Email Alerts with your email address.
  • Save to my folders

Share this Article

  • Email

    Thank you for your interest in spreading the word on Arteriosclerosis, Thrombosis, and Vascular Biology.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Abstract 45: Characterization of a Novel Integrin Binding Protein that is Essential for αIIbβ3 Outside-in Signaling and Hemostasis
    (Your Name) has sent you a message from Arteriosclerosis, Thrombosis, and Vascular Biology
    (Your Name) thought you would like to see the Arteriosclerosis, Thrombosis, and Vascular Biology web site.
  • Share on Social Media
    Abstract 45: Characterization of a Novel Integrin Binding Protein that is Essential for αIIbβ3 Outside-in Signaling and Hemostasis
    Binggang Xiang, Guoying Zhang, Shaojing Ye, Cai Huang, Jun Liu, Min Tao, Changgeng Ruan, Susan Smyth, Sidney Whiteheart and Zhenyu Li
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2015;35:A45, originally published August 11, 2015
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Arteriosclerosis, Thrombosis, and Vascular Biology

  • About ATVB
  • Instructions for Authors
  • AHA CME
  • Meeting Abstracts
  • Permissions
  • Email Alerts
  • Open Access Information
  • AHA Journals RSS
  • AHA Newsroom

Contact the Editorial Office:
email: atvb@atvb.org

Information for:
  • Advertisers
  • Subscribers
  • Subscriber Help
  • Institutions / Librarians
  • Institutional Subscriptions FAQ
  • International Users
American Heart Association Learn and Live
National Center
7272 Greenville Ave.
Dallas, TX 75231

Customer Service

  • 1-800-AHA-USA-1
  • 1-800-242-8721
  • Local Info
  • Contact Us

About Us

Our mission is to build healthier lives, free of cardiovascular diseases and stroke. That single purpose drives all we do. The need for our work is beyond question. Find Out More about the American Heart Association

  • Careers
  • SHOP
  • Latest Heart and Stroke News
  • AHA/ASA Media Newsroom

Our Sites

  • American Heart Association
  • American Stroke Association
  • For Professionals
  • More Sites

Take Action

  • Advocate
  • Donate
  • Planned Giving
  • Volunteer

Online Communities

  • AFib Support
  • Garden Community
  • Patient Support Network
  • Professional Online Network

Follow Us:

  • Follow Circulation on Twitter
  • Visit Circulation on Facebook
  • Follow Circulation on Google Plus
  • Follow Circulation on Instagram
  • Follow Circulation on Pinterest
  • Follow Circulation on YouTube
  • Rss Feeds
  • Privacy Policy
  • Copyright
  • Ethics Policy
  • Conflict of Interest Policy
  • Linking Policy
  • Diversity
  • Careers

©2018 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is a qualified 501(c)(3) tax-exempt organization.
*Red Dress™ DHHS, Go Red™ AHA; National Wear Red Day ® is a registered trademark.

  • PUTTING PATIENTS FIRST National Health Council Standards of Excellence Certification Program
  • BBB Accredited Charity
  • Comodo Secured