Calreticulin-integrin bidirectional signaling complex.
Calreticulin has multiple functions, diverse cellular locations, and putative isoforms. It likely maintains integrin avidity by binding alpha integrin cytoplasmic tails and is a surface lectin which triggers cell spreading. In the present study, we have immunocaptured a cell surface complex from B16 mouse melanoma cells which contains alpha 6 beta 1 integrin, two molecular forms of calreticulin, and KDEL docking protein (KDEL-R). One of the calreticulins, "endocalreticulin", a 52 kDa protein, does not become surface biotinylated, and is probably bound to alpha integrin cytoplasmic tails; it disappears when B16 cells adhere to laminin, and two ubiquitinated calreticulins appear. One ubiquitinated species, a 125 kDa protein, is restricted to focal contacts whereas a second species, a 75 kDa protein, is in focal contacts and surrounding plasma membrane; it also arises when cells bind non-specific surfaces. The other calreticulin, "ectocalreticulin", a 62 kDa protein, becomes surface biotinylated, is probably anchored to surface KDEL-R, and cooperates with alpha 6 beta 1 integrin, triggering cell spreading. The present results suggest a model in which calreticulin-integrin surface complex functions as a symbiotic unit, transmitting information in both directions across the plasma membrane.
Zhu
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Department of BioStructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington 06030-3705, USA.
Zelinka
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White
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Tanzer
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ML
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D037282:Calreticulin; D002448:Cell Adhesion; D004797:Enzyme-Linked Immunosorbent Assay; D016023:Integrins / Q000502:physiology*; D007536:Isomerism; D008545:Melanoma; D051379:Mice; D012261:Ribonucleoproteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D016023:Integrins; D012261:Ribonucleoproteins; D014452:Ubiquitins