Inhibition of SRY-calmodulin complex formation induces ectopic expression of ovarian cell markers in developing XY gonads

Sim, Helena, Argentaro, Anthony, Czech, Daniel P., Bagheri-Fam, Stefan, Sinclair, Andrew H., Koopman, Peter, Boizet-Bonhoure, Brigitte, Poulat, Francis and Harley, Vincent R. (2011) Inhibition of SRY-calmodulin complex formation induces ectopic expression of ovarian cell markers in developing XY gonads. Endocrinology, 152 7: 2883-2893. doi:10.1210/en.2010-1475


Author Sim, Helena
Argentaro, Anthony
Czech, Daniel P.
Bagheri-Fam, Stefan
Sinclair, Andrew H.
Koopman, Peter
Boizet-Bonhoure, Brigitte
Poulat, Francis
Harley, Vincent R.
Title Inhibition of SRY-calmodulin complex formation induces ectopic expression of ovarian cell markers in developing XY gonads
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
Publication date 2011-07-01
Sub-type Article (original research)
DOI 10.1210/en.2010-1475
Volume 152
Issue 7
Start page 2883
End page 2893
Total pages 11
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Collection year 2012
Language eng
Formatted abstract
The transcription factor sex-determining region of the Y chromosome (SRY) plays a key role in human sex determination, because mutations in SRY cause disorders of sex development in XY individuals. During gonadal development, Sry in pre-Sertoli cells activates Sox9 gene transcription, committing the fate of the bipotential gonad to become a testis rather than an ovary. The high-mobility group domain of human SRY contains two independent nuclear localization signals, one bound by calmodulin (CaM) and the other by importin-β. Although XY females carry SRY mutations in these nuclear localization signals that affect SRY nuclear import in transfected cells, it is not known whether these transport mechanisms are essential for gonadal development and sex determination. Here, we show that mouse Sry protein binds CaM and that a CaM antagonist reduces CaM binding, nuclear accumulation, and transcriptional activity of Sry in transfected cells. CaM antagonist treatment of cultured, sexually indifferent XY mouse fetal gonads led to reduced expression of the Sry target gene Sox9, defects in testicular cord formation, and ectopic expression of the ovarian markers Rspondin1 and forkhead box L2. These results indicate the importance of CaM for SRY nuclear import, transcriptional activity, testis differentiation, and sex determination.
Keyword Sex-determining region
Mobility group domain
Nuclear localization signals
Dna-binding
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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