Lack of tyrosylprotein sulfotransferase-2 activity results in altered sperm-egg interactions and loss of ADAM3 and ADAM6 in epididymal sperm

Matthew R. Marcello, Weitao Jia, Julie A. Leary, Kevin L. Moore, Janice Perry Evans

Research output: Contribution to journalArticle

Abstract

Tyrosine O-sulfation is a post-translational modification catalyzed by two tyrosylprotein sulfotransferases (TPST-1 and TPST-2) in the trans-Golgi network. Tpst2-deficient mice have male infertility, sperm motility defects, and possible abnormalities in sperm-egg membrane interactions. Studies here show that compared with wild-type sperm, fewer Tpst2-null sperm bind to the egg membrane, but more of these bound sperm progress to membrane fusion. Similar outcomes were observed with wild-type sperm treated with the anti-sulfotyrosine antibody PSG2. The increased extent of sperm-egg fusion is not due to a failure of Tpst2-null sperm to trigger establishment of the egg membrane block to polyspermy. Anti-sulfotyrosine staining of sperm showed localization similar to that of IZUMO1, a sperm protein that is essential for gamete fusion, but we detected little to no tyrosine sulfation of IZUMO1 and found that IZUMO1 expression and localization were normal in Tpst2-null sperm. Turning to a discovery-driven approach, we used mass spectrometry to characterize sperm proteins that associated with PSG2. This identified ADAM6, a member of the A disintegrin and A metalloprotease (ADAM) family; members of this protein family are associated with multiple sperm functions. Subsequent studies revealed that Tpst2-null sperm lack ADAM6 and ADAM3. Loss of ADAM3 is strongly associated with male infertility and is observed in knockouts of male germ line-specific endoplasmic reticulum-resident chaperones, raising the possibility that TPST-2 may function in quality control in the secretory pathway. These data suggest that TPST-2-mediated tyrosine O-sulfation participates in regulating the sperm surface proteome or membrane order, ultimately affecting male fertility.

Original languageEnglish (US)
Pages (from-to)13060-13070
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number15
DOIs
StatePublished - Apr 15 2011

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Sperm-Ovum Interactions
Spermatozoa
Membranes
Tyrosine
Fusion reactions
Disintegrins
Proteins
Metalloproteases
Proteome
Ovum
Quality control
Mass spectrometry
Male Infertility
Germ Cells
protein-tyrosine sulfotransferase
ADAM 3
Defects
thymidylyl(3'-5')-5'-thio-5'-deoxythymidine
Antibodies
trans-Golgi Network

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Lack of tyrosylprotein sulfotransferase-2 activity results in altered sperm-egg interactions and loss of ADAM3 and ADAM6 in epididymal sperm. / Marcello, Matthew R.; Jia, Weitao; Leary, Julie A.; Moore, Kevin L.; Evans, Janice Perry.

In: Journal of Biological Chemistry, Vol. 286, No. 15, 15.04.2011, p. 13060-13070.

Research output: Contribution to journalArticle

Marcello, Matthew R. ; Jia, Weitao ; Leary, Julie A. ; Moore, Kevin L. ; Evans, Janice Perry. / Lack of tyrosylprotein sulfotransferase-2 activity results in altered sperm-egg interactions and loss of ADAM3 and ADAM6 in epididymal sperm. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 15. pp. 13060-13070.
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