Go protein subunit Goα and the secretory process of the natriuretic peptide hormones ANF and BNP.
Expression of the G protein subunit Goα has been shown to be prominent in the atria of the rat heart and to be significantly associated with atrial natriuretic factor (ANF)-containing atrial-specific secretory granules by immunocytochemistry. In addition, differential expression profile analysis using oligonucleotide arrays has shown that the Goα isoform 1 (Goα1) is 2.3-fold more abundant in the atria than it is in the ventricles. In the present report, we show protein-protein interaction between Goα and ANF by yeast two-hybrid and by immunoprecipitation. A cardiac conditional Goα knockout model developed for the present study showed a 90% decrease in Goα expression and decreased atrial expression and ANF and brain natriuretic peptides (BNP) content. Expression of chromogranin A, a specific atrial granule core constituent, was not affected. Morphometric assessment of atrial tissue showed a very significant decrease in atrial-specific granule density as well as granule core electron density. Atrial electrical activity was not affected. The results obtained are compatible with the suggestion that Goα plays a role in ANF sorting during intracellular vectorial transport and with the presence of a mechanism that preserves the molar relationship between cellular ANF and BNP stores in the face of the decreased production of these hormones.
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Cassandra
C
Roeske
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Amy
A
Martinuk
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Asna
A
Choudhry
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Geoffrey N
GN
Hendy
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Michael
M
Gollob
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Qiuji
Q
Li
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Tina
T
Georgalis
Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4 Cardiovascular Endocrinology LaboratoryUniversity of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7Department of Pathology and Laboratory MedicineFaculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5Experimental Therapeutics and MetabolismMcGill University Health Centre-Research Institute, and Departments of Medicine, Physiology and Human Genetics, McGill University, Montreal, Quebec, CanadaToronto General Hospital200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4 adebold@bell.net.
Adolfo J
AJ
de Bold
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D015870:Gene Expression; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
ANF; G proteins; endocrine heart; hormone secretion; hormone storage