Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor.
Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed that bicarbonate mediates its effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.
Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Y
Y
Chen
M J
MJ
Cann
T N
TN
Litvin
V
V
Iourgenko
M L
ML
Sinclair
L R
LR
Levin
J
J
Buck
D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D020134:Catalytic Domain; D002460:Cell Line; D000458:Cyanobacteria / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D019143:Evolution, Molecular; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010802:Phylogeny; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D012995:Solubility; D013075:Sperm Capacitation; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D013737:Testis / Q000378:metabolism
D001639:Bicarbonates; D011994:Recombinant Proteins; D000242:Cyclic AMP; D000262:Adenylyl Cyclases