pH-dependent association of chromogranin A with secretory vesicle membrane and a putative membrane binding region of chromogranin A.
Chromogranin A is a low-affinity, high-capacity Ca2+ binding protein, postulated to be responsible for the Ca2+ buffering role of secretory vesicles, and has been found only in the soluble portions of the vesicular proteins. Contrary to the generally accepted notion of chromogranin A existing as a soluble matrix protein, chromogranin A bound to the secretory vesicle membrane at the intravesicular pH of 5.5 and freed from the membrane when the pH was raised to a more physiological pH of 7.5. Trypsin digestion studies of the vesicle membrane suggested that chromogranin A interacts with the protein component(s) on the intravesicular side of the membrane. Furthermore, in a study using 14 synthetic chromogranin A peptides which represent various portions of chromogranin A, a segment in the N-terminal region (residues 18-37) was shown to bind to the vesicle membrane in a pH-dependent manner. The pH-dependent vesicle membrane binding property of chromogranin A appears to be of fundamental physiological importance with regard to the potential roles of chromogranin A in secretory vesicle biogenesis, particularly in segregating secretory vesicle membranes from others in the trans-Golgi network, and also in transmitting extravesicular signals such as inositol 1,4,5-trisphosphate or inositol 1,3,4,5-tetrakisphosphate for Ca2+ release or uptake to the inside of vesicles.
Yoo
S H
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Laboratory of Cellular Biology, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002846:Chromatography, Affinity; D053379:Chromogranin A; D002864:Chromogranins / Q000737:chemistry / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000648:ultrastructure*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011189:Potassium Chloride; D051381:Rats; D014357:Trypsin / Q000378:metabolism
D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C506153:chromogranin A, rat; D011189:Potassium Chloride; D014357:Trypsin