title: Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition.
abstract: A unique characteristic of mammalian spermatozoa is that, upon ejaculation, they are unable to recognize and bind to an ovulated oocyte. These functional attributes are only realized following the cells' ascent of the female reproductive tract whereupon they undergo a myriad of biochemical and biophysical changes collectively referred to as 'capacitation'. We have previously shown that this functional transformation is, in part, engineered by the modification of the sperm surface architecture leading to the assembly and/or presentation of multimeric sperm-oocyte receptor complexes. In this study, we have extended our findings through the characterization of one such complex containing arylsulfatase A (ARSA), sperm adhesion molecule 1 (SPAM1) and the molecular chaperone, heat shock 70kDa protein 2 (HSPA2). Through the application of flow cytometry we revealed that this complex undergoes a capacitation-associated translocation to facilitate the repositioning of ARSA to the apical region of the human sperm head, a location compatible with a role in the mediation of sperm-zona pellucida (ZP) interactions. Conversely, SPAM1 appears to reorient away from the sperm surface, possibly reflecting its primary role in cumulus matrix dispersal preceding sperm-ZP recognition. The dramatic relocation of the complex was completely abolished by incubation of capacitating spermatozoa in exogenous cholesterol or broad spectrum protein kinase A (PKA) and tyrosine kinase inhibitors suggesting that it may be driven by alterations in membrane fluidity characteristics and concurrently by the activation of a capacitation-associated signal transduction pathway. Collectively these data afford novel insights into the sub-cellular localization and potential functions of multimeric protein complexes in human spermatozoa.
authors.affiliation: Reproductive Science Group, School of Environmental and Life Sciences, Discipline of Biological Sciences,  University of Newcastle, University Drive, Callaghan, NSW 2308,  Australia.
authors.forename: Kate A
authors.initials: KA
authors.lastname: Redgrove
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Anderson
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
authors.forename: Moira K
authors.initials: MK
authors.lastname: O'Bryan
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013075:Sperm Capacitation / Q000187:drug effects / Q000235:genetics*; D013077:Sperm Head / Q000187:drug effects / Q000378:metabolism*; D013084:Sperm-Ovum Interactions / Q000187:drug effects* / Q000235:genetics; D015044:Zona Pellucida / Q000187:drug effects / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D047428:Protein Kinase Inhibitors; D002784:Cholesterol; D002553:Cerebroside-Sulfatase; D006821:Hyaluronoglucosaminidase; C066852:hyaluronidase PH-20