LCP1 preferentially binds clasped αMβ2 integrin and attenuates leukocyte adhesion under flow

J Cell Sci. 2018 Nov 21;131(22):jcs218214. doi: 10.1242/jcs.218214.


Integrins are α/β heterodimers that interconvert between inactive and active states. In the active state the α/β cytoplasmic domains recruit integrin-activating proteins and separate the transmembrane and cytoplasmic (TMcyto) domains (unclasped TMcyto). Conversely, in the inactive state the α/β TMcyto domains bind integrin-inactivating proteins, resulting in the association of the TMcyto domains (clasped TMcyto). Here, we report the isolation of integrin cytoplasmic tail interactors using either lipid bicelle-incorporated integrin TMcyto domains (α5, αM, αIIb, β1, β2 and β3 integrin TMcyto) or a clasped, lipid bicelle-incorporated αMβ2 TMcyto. Among the proteins found to preferentially bind clasped rather than the isolated αM and β2 subunits was L-plastin (LCP1, also known as plastin-2), which binds to and maintains the inactive state of αMβ2 integrin in vivo and thereby regulates leukocyte adhesion to integrin ligands under flow. Our findings offer a global view on cytoplasmic proteins interacting with different integrins and provide evidence for the existence of conformation-specific integrin interactors.

Keywords: Integrin inactivator; Integrin interactome; LCP1; Leukocyte adhesion; Proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / physiology*
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • HEK293 Cells
  • Humans
  • Leukocytes / cytology*
  • Leukocytes / metabolism*
  • Macrophage-1 Antigen / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • RAW 264.7 Cells


  • LCP1 protein, human
  • Macrophage-1 Antigen
  • Microfilament Proteins
  • Lcp1 protein, mouse