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Particulate Adenylate Cyclase Plays a Key Role in Human Sperm Olfactory Receptor-mediated Chemotaxis*
Marc Spehr,
Katlen Schwane¶,
Jeffrey A. Riffell||,
Jon Barbour¶,
Richard K. Zimmer||**,
Eva M. Neuhaus¶, , and
Hanns Hatt¶
Department of Anatomy and Neurobiology, University of Maryland, Baltimore, Maryland 21201, the ¶Lst. Zellphysiologie, Ruhr-Universität Bochum, Universitätsstrasse 150, 44780 Bochum, Germany, the ||Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095-1606, and the **Department of Neurosciences, Brain Research Institute, University of California, Los Angeles, California 90095-1606
Abstract:
Human sperm chemotaxis is a critical component of the fertilizationprocess, but the molecular basis for this behavior remains unclear.Recent evidence shows that chemotactic responses depend on activationof the sperm olfactory receptor, hOR17-4. Certain floral scents,including bourgeonal, activate hOR17-4, trigger pronounced Ca2+fluxes, and evoke chemotaxis. Here, we provide evidence thathOR17-4 activation is coupled to a cAMP-mediated signaling cascade.Multidimensional protein identification technology was usedto identify potential components of a G-protein-coupled cAMPtransduction pathway in human sperm. These products includedvarious membrane-associated adenylate cyclase (mAC) isoformsand the Golf-subunit. Using immunocytochemistry, specific mACisoforms were localized to particular cell regions. WhereasmAC III occurred in the sperm head and midpiece, mAC VIII wasdistributed predominantly in the flagellum. In contrast, Golfwas found mostly in the flagellum and midpiece. The observedspatial distribution patterns largely correspond to the spatiotemporalcharacter of hOR17-4-induced Ca2+ changes. Behavioral and Ca2+signaling responses of human sperm to bourgeonal were bioassayedin the presence, or absence, of the adenylate cyclase antagonistSQ22536. This specific agent inhibits particulate AC, but notsoluble AC, activation. Upon incubation with SQ22536, cellsceased to exhibit Ca2+ signaling, chemotaxis, and hyperactivation(faster swim speed and flagellar beat rate) in response to bourgeonal.Particulate AC is therefore required for induction of hOR17-4-mediatedhuman sperm behavior and represents a promising target for futuredesign of contraceptive drugs.
Received for publication April 8, 2004.
Revision received July 6, 2004.
* This work was supported by the Alma und Heinrich Vogelsang Stiftung.The costs of publication of this article were defrayed in partby the payment of page charges. This article must thereforebe hereby marked "advertisement" in accordance with 18 U.S.C.Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. Anatomy and Neurobiology, School of Medicine, University of Maryland, 685 West Baltimore St., Baltimore, MD 21201. Tel.: 410-706-8921; Fax: 410-706-2512; E-mail: mspeh001{at}umaryland.edu.
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,
Katlen Schwane¶,
Jeffrey A. Riffell||,
Jon Barbour¶,
Richard K. Zimmer||**,
Eva M. Neuhaus¶, , and
Hanns Hatt¶
To whom correspondence should be addressed: Dept. Anatomy and Neurobiology, School of Medicine, University of Maryland, 685 West Baltimore St., Baltimore, MD 21201. Tel.: 410-706-8921; Fax: 410-706-2512; E-mail: 
