Parp2 is required for the differentiation of post-meiotic germ cells: identification of a spermatid-specific complex containing Parp1, Parp2, TP2 and HSPA2.
Spermiogenesis is a complex male germ cell post-meiotic differentiation process characterized by dramatic changes in chromatin structure and function, including chromatin condensation, transcriptional inhibition and the sequential replacement of histones by transition proteins and protamines. Recent advances, in mammalian cells, suggest a possible role of poly(ADP-ribosyl)ation catalyzed by Parp1 and/or Parp2 in this process. We have recently reported severely compromised spermiogenesis in Parp2-deficient mice characterized by a marked delay in nuclear elongation whose molecular mechanisms remain however unknown. Here, using in vitro protein-protein interaction assays, we show that Parp2 interacts significantly with both the transition protein TP2 and the transition chaperone HSPA2, whereas Parp1 binds weakly to HSPA2. Parp2-TP2 interaction is partly mediated by poly(ADP-ribosyl)ation. Only Parp1 poly(ADP-ribosyl)ates HSPA2. In addition, a detailed analysis of spermatid maturation in Parp2-deficient mice, combining immunohistochemistry and electron microscopic approaches, reveals a loss of spermatids expressing TP2, a defect in chromatin condensation and abnormal formation of the manchette microtubules that, together, contribute to spermatid-specific cell death. In conclusion, we propose both Parps as new participants of a spermatid-specific protein complex involved in genome reorganization throughout spermiogenesis.
Quénet
Delphine
D
IREBS-FRE 3211, Ecole Supérieure de Biotechnologie de Strasbourg, F-67412 Illkirch cedex, France.
Mark
Manuel
M
Govin
Jérôme
J
van Dorsselear
A
A
Schreiber
Valérie
V
Khochbin
Saadi
S
Dantzer
Françoise
F
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D013087:Spermatids / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D009687:Nuclear Proteins; C489505:Tnp2 protein, mouse; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse