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Abstract
In mature sperm, cAMP plays an important role as a second
messenger regulating functions that include capacitation,
the acrosome reaction, motility, and in some cases,
chemosensing. We have cloned from mouse testis a novel
calmodulin-stimulated cyclic
nucleotide phosphodiesterase 1A isoform, Pde1a_v7.
(mmPDE1A7) which arises from an
alternative transcription start in the cyclic nucleotide
phosphodiesterase 1A gene. The open
reading frame is predicted to encode a polypeptide with a
molecular mass of 52 kDa. Two
further variants of this form which contain two additional
new exons arise from alternative
splicing. Analysis of testis cDNA by real time PCR
indicates that the Pde1A_v7 transcript
variant is the most abundant.
The PDE1A_v7 protein uniquely lacks the first
amino-terminal calmodulin-binding
domain, but does possess an inhibitory domain and a second
calmodulin-binding site shared
with other variants. In vitro translation of the
corresponding Pde1a_v7 cDNA produced a 52
kDa polypeptide having cyclic nucleotide hydrolytic
activity, which was stimulated three-fold
by calcium-bound calmodulin.
Immunoprecipitation of cyclic nucleotide phosphodiesterase
1 activity from detergent
extracts of mouse sperm revealed a major protein of the
size expected for PDE1A_v7 and the
Immunocytochemical staining for cyclic nucleotide
phosphodiesterase 1A in mouse sperm
showed intense immunoreactivity in the tail only. These
observations along with the PCR data
strongly suggest that this new variant PDE1A_v7 is the
major form of cyclic nucleotide
phosphodiesterase 1A expressed in mature sperm and
therefore likely to play an important role
in cyclic nucleotide regulation of mature sperm function.
Key words:
Calcium
Signal transduction
Sperm capacitation
Sperm maturation
Sperm motility and transport
This article has been cited by other articles:
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A. T. Bender and J. A. Beavo Cyclic Nucleotide Phosphodiesterases: Molecular Regulation to Clinical Use Pharmacol. Rev., September 1, 2006; 58(3): 488 - 520. [Abstract] [Full Text] [PDF] |
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