TCP-11, the product of a mouse t-complex gene, plays a role in stimulation of capacitation and inhibition of the spontaneous acrosome reaction.
Tcp-11 is a candidate for a distorter gene within the t-complex on mouse chromosome 17; although t-complex genes appear to affect sperm function, relatively little is known about mechanisms whereby these genes might play a specific physiological role. We present evidence that the protein TCP-11 is found on the surface of mature epididymal spermatozoa. Although detected on both the acrosomal cap region of the head and the flagellum of acrosome-intact cells, it is absent from the heads of acrosome-reacted cells. When epididymal spermatozoa were incubated in the presence of anti-TCP-11 IgG Fab fragments for a total of 120 min and assessed using chlortetracycline fluorescence, we observed a stimulation of capacitation and an inhibition of spontaneous acrosome loss, suggestive of enhanced fertility compared with untreated suspensions. In vitro fertilization experiments confirmed that Fab-treated suspensions became fertile more quickly and then maintained high fertility. Because these responses were remarkably similar to those obtained using the TRH-related peptide FPP (fertilization promoting peptide; pGlu-Glu-ProNH2) and adenosine, we investigated responses to Fab fragments, FPP, and adenosine. Results indicated that the Fab fragments appear to work at the same extracellular site as FPP, one that is distinct from the adenosine site of action. Further evidence for this conclusion was obtained using pGlu-Gln-ProNH2, an FPP-related tripeptide known to competitively inhibit responses to FPP; as with FPP, pGlu-Glu-ProNH2 inhibited the stimulatory effect of Fab fragments in a concentration-dependent manner. From these results we suggest that TCP-11 may be the receptor for FPP and that the adenylate clyclase/cyclic AMP pathway may be the signal transduction pathway activated by interactions between extracellular effector molecules (e.g., Fab fragments or FPP acting as an agonist) and TCP-11. A mechanism such as this that promotes capacitation but inhibits spontaneous acrosome loss in vivo would play a very important role by helping to maximize the fertilizing potential of the few spermatozoa that reach the site of fertilization. The fact that there is a human homolog of Tcp-11 suggests that this gene could play an important role in regulation of human, as well as mouse, sperm function.
Fraser
L R
LR
Anatomy and Human Biology Group, King's College, Strand, London, United Kingdom.
Hosseini
R
R
Hanyalogou
A
A
Talmor
A
A
Dudley
R K
RK
D000177:Acrosome / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology / Q000502:physiology; D007074:Immunoglobulin G / Q000494:pharmacology / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D012044:Regression Analysis; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
D004268:DNA-Binding Proteins; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C533399:TCP11 protein, human; C533400:Tcp11 protein, mouse; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases