Calreticulin couples calcium release and calcium influx in integrin-mediated calcium signaling.
The engagement of integrin alpha7 in E63 skeletal muscle cells by laminin or anti-alpha7 antibodies triggered transient elevations in the intracellular free Ca(2+) concentration that resulted from both inositol triphosphate-evoked Ca(2+) release from intracellular stores and extracellular Ca(2+) influx through voltage-gated, L-type Ca(2+) channels. The extracellular domain of integrin alpha7 was found to associate with both ectocalreticulin and dihydropyridine receptor on the cell surface. Calreticulin appears to also associate with cytoplasmic domain of integrin alpha7 in a manner highly dependent on the cytosolic Ca(2+) concentration. It appeared that intracellular Ca(2+) release was a prerequisite for Ca(2+) influx and that calreticulin associated with the integrin cytoplasmic domain mediated the coupling of between the Ca(2+) release and Ca(2+) influx. These findings suggest that calreticulin serves as a cytosolic activator of integrin and a signal transducer between integrins and Ca(2+) channels on the cell surface.
Kwon
M S
MS
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, Korea.
Park
C S
CS
Choi
K
K
Ahnn
J
J
Kim
J I
JI
Eom
S H
SH
Kaufman
S J
SJ
Song
W K
WK
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D037282:Calreticulin; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005470:Fluorometry; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D039001:Integrin alpha Chains; D015640:Ion Channel Gating; D007797:Laminin / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D051381:Rats; D012261:Ribonucleoproteins / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000906:Antibodies; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D039001:Integrin alpha Chains; D007797:Laminin; D012261:Ribonucleoproteins; C085725:integrin alpha7; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium