A sperm-specific Na+/H+ exchanger (sNHE) is critical for expression and in vivo bicarbonate regulation of the soluble adenylyl cyclase (sAC)

Dan Wang, Jie Hu, I. Alexandru Bobulescu, Timothy A. Quill, Paul McLeroy, Orson W. Moe, David L. Garbers

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

We previously identified a sperm-specific Na+/H+ exchanger (sNHE) principally localized to the flagellum. Disruption of the sNHE gene in mice resulted in absolute male infertility associated with a complete loss of sperm motility. Here, we show that the sNHE-null spermatozoa fail to develop the cAMP-dependent protein tyrosine phosphorylation that coincides with the functional maturation occurring upon incubation in capacitating conditions in vitro. Both the sperm motility defect and the lack of induced protein tyrosine phosphorylation are rescued by the addition of cell-permeable cAMP analogs, suggesting that cAMP metabolism is impaired in spermatozoa lacking sNHE. Our analyses of the bicarbonate-dependent soluble adenylyl cyclase (sAC) signaling pathway in sNHE-null sperm cells reveal that sNHE is required for the expression of full-length sAC, and that it is important for the bicarbonate stimulation of sAC activity in spermatozoa. Furthermore, both codependent expression and coimmunoprecipitation experiments indicate that sNHE and sAC associate with each other. Thus, these two proteins appear to be components of a signaling complex at the sperm flagellar plasma membrane. We propose that the formation of this complex efficiently modulates intracellular pH and bicarbonate levels through the rapid and effective control of sAC and sNHE activities to facilitate sperm motility regulation.

Original languageEnglish (US)
Pages (from-to)9325-9330
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number22
DOIs
StatePublished - May 29 2007

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Sodium-Hydrogen Antiporter
Bicarbonates
Adenylyl Cyclases
Spermatozoa
Sperm Motility
Tyrosine
Phosphorylation
Null Lymphocytes
Proteins
Flagella
Male Infertility
Cell Membrane

Keywords

  • cAMP
  • Sperm motility

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A sperm-specific Na+/H+ exchanger (sNHE) is critical for expression and in vivo bicarbonate regulation of the soluble adenylyl cyclase (sAC). / Wang, Dan; Hu, Jie; Bobulescu, I. Alexandru; Quill, Timothy A.; McLeroy, Paul; Moe, Orson W.; Garbers, David L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 22, 29.05.2007, p. 9325-9330.

Research output: Contribution to journalArticle

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