title: The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition.
abstract: A common defect encountered in the spermatozoa of male infertility patients is an idiopathic failure of sperm-egg recognition. In order to resolve the molecular basis of this condition we have compared the proteomic profiles of spermatozoa exhibiting an impaired capacity for sperm-egg recognition with normal cells using label free mass spectrometry (MS)-based quantification. This analysis indicated that impaired sperm-zona binding was associated with reduced expression of the molecular chaperone, heat shock 70 kDa protein 2 (HSPA2), from the sperm proteome. Western blot analysis confirmed this observation in independent patients and demonstrated that the defect did not extend to other members of the HSP70 family. HSPA2 was present in the acrosomal domain of human spermatozoa as a major component of 5 large molecular mass complexes, the most dominant of which was found to contain HSPA2 in close association with just two other proteins, sperm adhesion molecule 1 (SPAM1) and arylsulfatase A (ARSA), both of which that have previously been implicated in sperm-egg interaction. The interaction between SPAM1, ARSA and HSPA2 in a multimeric complex mediating sperm-egg interaction, coupled with the complete failure of this process when HSPA2 is depleted in infertile patients, provides new insights into the mechanisms by which sperm function is impaired in cases of male infertility.
authors.affiliation: Priority Research Centre in Reproductive Science, School of Environmental and Life Sciences, Discipline of Biological Sciences, The University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Kate A
authors.initials: KA
authors.lastname: Redgrove
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
authors.forename: Mark A
authors.initials: MA
authors.lastname: Baker
authors.forename: Louise
authors.initials: L
authors.lastname: Hetherington
authors.forename: Gordon
authors.initials: G
authors.lastname: Baker
authors.forename: De-Yi
authors.initials: DY
authors.lastname: Liu
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
mesh_terms: D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002553:Cerebroside-Sulfatase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D011485:Protein Binding; D013084:Sperm-Ovum Interactions / Q000235:genetics / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D002553:Cerebroside-Sulfatase; D006821:Hyaluronoglucosaminidase; C066852:hyaluronidase PH-20