Phosphatidylinositol 4,5-bisphosphate clusters the cell adhesion molecule CD44 and assembles a specific CD44-Ezrin heterocomplex, as revealed by small angle neutron scattering

Xiaodong Chen, Jahan Ali Khajeh, Jeong Ho Ju, Yogesh K Gupta, Christopher B. Stanley, Changwoo Do, William T. Heller, Aneel K. Aggarwal, David J.E. Callaway, Zimei Bu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The cell adhesion molecule CD44 regulates diverse cellular functions, including cell-cell and cell-matrix interaction, cell motility, migration, differentiation, and growth. In cells, CD44 co-localizes with the membrane-cytoskeleton adapter protein Ezrin that links the CD44 assembled receptor signaling complexes to the cytoskeletal actin network, which organizes the spatial and temporal localization of signaling events. Here we report that the cytoplasmic tail of CD44 (CD44ct) is largely disordered. Upon binding to the signaling lipid phosphatidylinositol 4,5-bisphosphate (PIP2), CD44ct clusters into aggregates. Further, contrary to the generally accepted model, CD44ct does not bind directly to the FERM domain of Ezrin or to the full-length Ezrin but only forms a complex with FERM or with the full-length Ezrin in the presence of PIP2. Using contrast variation small angle neutron scattering, we show that PIP2 mediates the assembly of a specific heterotetramer complex of CD44ct with Ezrin. This study reveals the role of PIP2 in clustering CD44 and in assembling multimeric CD44-Ezrin complexes. We hypothesize that polyvalent electrostatic interactions are responsible for the assembly of CD44 clusters and the multimeric PIP2-CD44-Ezrin complexes.

Original languageEnglish (US)
Pages (from-to)6639-6652
Number of pages14
JournalJournal of Biological Chemistry
Volume290
Issue number10
DOIs
StatePublished - Mar 6 2015
Externally publishedYes

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Small Angle Scattering
Neutrons
Cell Adhesion Molecules
Neutron scattering
Phosphatidylinositols
Cell Movement
Coulomb interactions
ezrin
Cytoskeleton
Static Electricity
Cell Communication
Cluster Analysis
Actins
Membranes
Lipids
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Phosphatidylinositol 4,5-bisphosphate clusters the cell adhesion molecule CD44 and assembles a specific CD44-Ezrin heterocomplex, as revealed by small angle neutron scattering. / Chen, Xiaodong; Khajeh, Jahan Ali; Ju, Jeong Ho; Gupta, Yogesh K; Stanley, Christopher B.; Do, Changwoo; Heller, William T.; Aggarwal, Aneel K.; Callaway, David J.E.; Bu, Zimei.

In: Journal of Biological Chemistry, Vol. 290, No. 10, 06.03.2015, p. 6639-6652.

Research output: Contribution to journalArticle

Chen, Xiaodong ; Khajeh, Jahan Ali ; Ju, Jeong Ho ; Gupta, Yogesh K ; Stanley, Christopher B. ; Do, Changwoo ; Heller, William T. ; Aggarwal, Aneel K. ; Callaway, David J.E. ; Bu, Zimei. / Phosphatidylinositol 4,5-bisphosphate clusters the cell adhesion molecule CD44 and assembles a specific CD44-Ezrin heterocomplex, as revealed by small angle neutron scattering. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 10. pp. 6639-6652.
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