Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration

View ORCID ProfilePontus Nordenfelt, Travis I. Moore, Shalin B. Mehta , Joseph Mathew Kalappurakkal, Vinay Swaminathan, Nobuyasu Koga, Talley J. Lambert, David Baker, Jennifer C. Waters, Rudolf Oldenbourg, Tomomi Tani, Satyajit Mayor, View ORCID ProfileClare M. Waterman, View ORCID ProfileTimothy A. Springer
doi: https://doi.org/10.1101/071936
Pontus Nordenfelt
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
2Physiology Course, Marine Biological Laboratory, Woods Hole MA, USA
3Program in Cellular and Molecular Medicine, Children’s Hospital, and Department of Biological Chemistry and Molecular Pharmacology and Medicine, Harvard Medical School, Boston MA, USA
6Current address: Division of Infection Medicine, Lund University, Lund, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pontus Nordenfelt
Travis I. Moore
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
3Program in Cellular and Molecular Medicine, Children’s Hospital, and Department of Biological Chemistry and Molecular Pharmacology and Medicine, Harvard Medical School, Boston MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shalin B. Mehta
4Eugene Bell Center, Marine Biological Laboratory, Woods Hole MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph Mathew Kalappurakkal
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
2Physiology Course, Marine Biological Laboratory, Woods Hole MA, USA
5National Center for Biological Sciences, Bangalore, IN
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vinay Swaminathan
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
2Physiology Course, Marine Biological Laboratory, Woods Hole MA, USA
7Cell Biology and Physiology Center, NHLBI, NIH, Bethesda MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nobuyasu Koga
8University of Washington, Seattle, WA and Howard Hughes Medical Institute
9Current address: Institute for Molecular Science, Myodaiji, Okazaki, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Talley J. Lambert
10Department of Cell Biology, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Baker
8University of Washington, Seattle, WA and Howard Hughes Medical Institute
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer C. Waters
10Department of Cell Biology, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rudolf Oldenbourg
4Eugene Bell Center, Marine Biological Laboratory, Woods Hole MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomomi Tani
4Eugene Bell Center, Marine Biological Laboratory, Woods Hole MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satyajit Mayor
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
2Physiology Course, Marine Biological Laboratory, Woods Hole MA, USA
5National Center for Biological Sciences, Bangalore, IN
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clare M. Waterman
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
2Physiology Course, Marine Biological Laboratory, Woods Hole MA, USA
7Cell Biology and Physiology Center, NHLBI, NIH, Bethesda MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Clare M. Waterman
Timothy A. Springer
1Whitman Center, Marine Biological Laboratory, Woods Hole MA, USA
2Physiology Course, Marine Biological Laboratory, Woods Hole MA, USA
3Program in Cellular and Molecular Medicine, Children’s Hospital, and Department of Biological Chemistry and Molecular Pharmacology and Medicine, Harvard Medical School, Boston MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy A. Springer
  • For correspondence: Springer@crystal.harvard.edu Timothy.springer@childrens.harvard.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin head, known from crystal structures, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid head of the full integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin, and measure orientation with fluorescence polarization microscopy. Dependent on coupling to the cytoskeleton, integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. We have developed a method that places atomic, ~Å structures of cell surface receptors in the context of functional, cellular length-scale, ~μm measurements and shows that rotation and tilt of cell surface receptors relative to the membrane plane can be restrained by interactions with other cellular components.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 19, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Pontus Nordenfelt, Travis I. Moore, Shalin B. Mehta , Joseph Mathew Kalappurakkal, Vinay Swaminathan, Nobuyasu Koga, Talley J. Lambert, David Baker, Jennifer C. Waters, Rudolf Oldenbourg, Tomomi Tani, Satyajit Mayor, Clare M. Waterman, Timothy A. Springer
bioRxiv 071936; doi: https://doi.org/10.1101/071936
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Pontus Nordenfelt, Travis I. Moore, Shalin B. Mehta , Joseph Mathew Kalappurakkal, Vinay Swaminathan, Nobuyasu Koga, Talley J. Lambert, David Baker, Jennifer C. Waters, Rudolf Oldenbourg, Tomomi Tani, Satyajit Mayor, Clare M. Waterman, Timothy A. Springer
bioRxiv 071936; doi: https://doi.org/10.1101/071936

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3513)
  • Biochemistry (7359)
  • Bioengineering (5338)
  • Bioinformatics (20306)
  • Biophysics (10034)
  • Cancer Biology (7763)
  • Cell Biology (11333)
  • Clinical Trials (138)
  • Developmental Biology (6444)
  • Ecology (9968)
  • Epidemiology (2065)
  • Evolutionary Biology (13346)
  • Genetics (9366)
  • Genomics (12598)
  • Immunology (7719)
  • Microbiology (19060)
  • Molecular Biology (7452)
  • Neuroscience (41108)
  • Paleontology (300)
  • Pathology (1233)
  • Pharmacology and Toxicology (2141)
  • Physiology (3171)
  • Plant Biology (6869)
  • Scientific Communication and Education (1275)
  • Synthetic Biology (1899)
  • Systems Biology (5320)
  • Zoology (1090)