puc-header

Acto-Myosin Driven Functional Nanoclusters of GPI-Anchored Proteins Are Generated by Integrin Receptor Signaling

112 Pages Posted: 9 Apr 2018 Sneak Peek Status: Published

See all articles by Joseph Mathew Kalappurakkai

Joseph Mathew Kalappurakkai

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

Anupama Ambika Anilkumar

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

Chandrima Patra

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

Thomas S. van Zanten

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

Michael P. Sheetz

National University of Singapore (NUS) - Mechanobiology Institute (MBI)

Satyajit Mayor

Tata Institute of Fundamental Research (TIFR) - Department of Cellular Organization and Signaling

More...

Abstract

GPI-anchored protein (GPI-AP) nanoclusters are generated by cortical acto-myosin activity. While our understanding of the physical principles behind this process is emerging, the molecular machinery required for the generation of these nanoclusters is unknown. Here, we show that ligand-mediated membrane receptor signaling triggers nanocluster formation. Both soluble and surface-tethered RGD ligands bind the β1- integrin receptor and activate focal adhesion and src- kinases, resulting in RhoA signaling. This cascade ultimately triggers actin-nucleation via specific formins, driving nanoclustering of both GPI-APs and a model transmembrane protein with an actin binding domain. Integrin signaling concurrently results in talin mediated activation of vinculin. This is necessary for the coupling of the dynamic actin machinery to the inner leaflet driving GPI-AP nanoclustering. Disruption of GPI-AP nanoclustering in either GPI-anchor remodeling mutants or in cells that express vinculin mutants, provide evidence that these nanoclusters are necessary for activating cell spreading, a hallmark of integrin function.

Suggested Citation

Kalappurakkai, Joseph Mathew and Anilkumar, Anupama Ambika and Patra, Chandrima and van Zanten, Thomas S. and Sheetz, Michael P. and Mayor, Satyajit, Acto-Myosin Driven Functional Nanoclusters of GPI-Anchored Proteins Are Generated by Integrin Receptor Signaling (2018). Available at SSRN: https://ssrn.com/abstract=3155624 or http://dx.doi.org/10.2139/ssrn.3155624
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Joseph Mathew Kalappurakkai

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

STCS, TIFR, 1, Homi Bhabha Road
Colaba
Mumbai, 400005
India

Anupama Ambika Anilkumar

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

STCS, TIFR, 1, Homi Bhabha Road
Colaba
Mumbai, 400005
India

Chandrima Patra

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

STCS, TIFR, 1, Homi Bhabha Road
Colaba
Mumbai, 400005
India

Thomas S. Van Zanten

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Science

STCS, TIFR, 1, Homi Bhabha Road
Colaba
Mumbai, 400005
India

Michael P. Sheetz

National University of Singapore (NUS) - Mechanobiology Institute (MBI) ( email )

5A Engineering Drive 1
T-Lab, #10-01
117411
Singapore

Satyajit Mayor (Contact Author)

Tata Institute of Fundamental Research (TIFR) - Department of Cellular Organization and Signaling

STCS, TIFR, 1, Homi Bhabha Road
Colaba
Mumbai, 400005
India

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
352
Downloads
10