1. Physics of Living Systems
  2. Cell Biology
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Phase transitions of multivalent proteins can promote clustering of membrane receptors

  1. Sudeep Banjade
  2. Michael K Rosen  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States
Research Article
  • Cited 239
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Cite this article as: eLife 2014;3:e04123 doi: 10.7554/eLife.04123


Clustering of proteins into micrometer-sized structures at membranes is observed in many signaling pathways. Most models of clustering are specific to particular systems, and relationships between physical properties of the clusters and their molecular components are not well understood. We report biochemical reconstitution on supported lipid bilayers of protein clusters containing the adhesion receptor Nephrin, and its cytoplasmic partners, Nck and N-WASP. With Nephrin attached to the bilayer, multivalent interactions enable these proteins to polymerize on the membrane surface and undergo two-dimensional phase separation, producing micrometer-sized clusters. Dynamics and thermodynamics of the clusters are modulated by the valencies and affinities of the interacting species. In the presence of the Arp2/3 complex, the clusters assemble actin filaments, suggesting that clustering of regulatory factors could promote local actin assembly at membranes. Interactions between multivalent proteins could be a general mechanism for cytoplasmic adaptor proteins to organize membrane receptors into micrometer-scale signaling zones.

Article and author information

Author details

  1. Sudeep Banjade

    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael K Rosen

    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Anthony A Hyman, Max Planck Institute of Molecular Cell Biology and Genetics, Germany

Publication history

  1. Received: July 22, 2014
  2. Accepted: October 16, 2014
  3. Accepted Manuscript published: October 16, 2014 (version 1)
  4. Version of Record published: November 20, 2014 (version 2)


© 2014, Banjade & Rosen

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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