Chromogranin A fragments modulate cell adhesion. Identification and characterization of a pro-adhesive domain.
Although several functions have been suggested for chromogranin A, a glycoprotein secreted by many neuroendocrine cells, the physiological role of this protein and of its proteolytic fragments has not been established. We have found that mixtures of chromogranin A fragments can inhibit fibroblast adhesion. The anti-adhesive activity was converted into pro-adhesive activity by limited trypsin treatment. Pro-adhesive effects were observed also with recombinant N-terminal fragments corresponding to residues 1-78 and 1-115 and with a synthetic peptide encompassing the residues 7-57. These fragments induced adhesion and spreading of fibroblasts on plates coated with collagen I or IV, laminin, fetal calf serum (FCS) but not on bovine serum albumin. The long incubation time required for adhesion assays (4 h) and the FCS requirements for optimal adhesion suggest that the adhesive activity is likely indirect and requires other proteins present in the FCS or made by the cells. These findings suggest that chromogranin A and its fragments could play a role in the regulation of cell adhesion. Since chromogranin A is concentrated and stored within granules and rapidly released by neuroendocrine cells and neurons after an appropriate stimulus, this protein could be important for the local control of cell adhesion by stimulated cells.
Gasparri
A
A
Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan, Italy.
Sidoli
A
A
Sanchez
L P
LP
Longhi
R
R
Siccardi
A G
AG
Marchisio
P C
PC
Corti
A
A
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D019012:Integrin beta1; D010446:Peptide Fragments; C506155:chromogranin A, mouse; C506153:chromogranin A, rat