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Calreticulin-integrin bidirectional signaling complex

Q Zhu1, P Zelinka, T White

  • 1Department of BioStructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington 06030-3705, USA.

Biochemical and Biophysical Research Communications
|March 17, 1997
PubMed

Insights

Calreticulin forms a surface complex with integrins, influencing cell adhesion and spreading. This complex facilitates bidirectional communication across the plasma membrane, revealing new insights into cell surface interactions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Calreticulin exhibits diverse functions and cellular locations.
  • It is implicated in maintaining integrin avidity and triggering cell spreading.
  • Calreticulin's role in cell surface complexes requires further elucidation.

Purpose of the Study:

  • To investigate the composition and function of calreticulin-containing cell surface complexes.
  • To characterize the distinct molecular forms of calreticulin involved in cell adhesion and spreading.
  • To elucidate the interaction between calreticulin, integrins, and KDEL docking protein (KDEL-R).

Main Methods:

  • Immunocapture of cell surface complexes from B16 mouse melanoma cells.
  • Surface biotinylation to identify cell surface-associated calreticulin.
  • Analysis of calreticulin localization and modification upon cell adhesion to laminin and non-specific surfaces.

Main Results:

  • A cell surface complex containing alpha 6 beta 1 integrin, two calreticulin forms, and KDEL-R was identified.
  • "Endocalreticulin" (52 kDa) binds to integrin cytoplasmic tails and disappears upon cell adhesion.
  • Ubiquitinated calreticulins (125 kDa and 75 kDa) appear during adhesion and are localized to focal contacts and plasma membrane.
  • "Ectocalreticulin" (62 kDa) is surface-biotinylated, anchored to KDEL-R, and cooperates with integrins to promote cell spreading.

Conclusions:

  • Calreticulin-integrin complexes function as a unit, mediating bidirectional transmembrane signaling.
  • Distinct calreticulin isoforms play specific roles in cell adhesion, spreading, and focal contact formation.
  • The findings propose a model for calreticulin's involvement in cell surface dynamics and communication.

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