Abstract
Sperm chemotaxis toward the egg plays a critical role in fertilization; however, the underlying mechanisms remain poorly understood. Spehr et al ., who recently showed that human sperm exhibited chemotaxis to the floral scent bourgeonal [which binds the olfactory receptor (OR) protein hOR17-4, thereby activating an adenosine 3′,5′-monophosphate (cAMP)-mediated pathway, eliciting Ca 2+ influx, and modifying flagellar beating], further investigated the mechanisms linking hOR17-4 activation to changes in sperm swimming. The authors used a multidimensional protein identification technology (MudPIT) approach based on two-dimensional liquid chromatography and mass spectroscopy to show that human spermatazoa expressed the G olf "olfactory specific" heterotrimeric guanine nucleotide-binding protein α subunit, as well as all nine mammalian isoforms of membrane-bound adenylyl cyclase (mAC). hOR17-4 expression, previously determined on the basis of functional assays, was confirmed as well. Immunofluorescence analysis for G olf , mAC III, and mAC VIII revealed that mAC VIII was localized to the flagellum, whereas mAC III was localized to the head and midpiece. mAC localization depended on acrosome status and showed a ringlike distribution in sperm that had not undergone the acrosome reaction and spreading through the heads of acrosome-reacted spermatazoa. G olf was found in the tail and midpiece. Ca 2+ signals elicited by bourgeonal originated in the midpiece before spreading to the head. Pharmacological analysis indicated that both the Ca 2+ signal and behavioral responses to bourgeonal depended on mAC and not on soluble AC (which has been identified in mammalian sperm). Thus, membrane-associated AC appears to be critically involved in Ca 2+ influx and sperm chemotaxis. M. Spehr, K. Schwane, J. A. Riffell, J. Barbour, R. K. Zimmer, E. M. Neuhaus, H. Hatt, Particulate adenylate cyclase plays a key role in human sperm olfactory receptor-mediated chemotaxis. J. Biol. Chem . 279 , 40194-40203 (2004). [Abstract] [Full Text]
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