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J Biol Chem, Vol. 274, Issue 2, 770-775, January 8, 1999
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From Proliferation and differentiation of progenitor
stem cells are mainly controlled by diffusible and adhesion molecules.
Stem cell factor (SCF), an essential regulator of spermatogenesis
produced by Sertoli cells, utilize both modes of cell to cell
communication. Indeed, SCF exists in soluble (SCFs) and membrane-bound
(SCFm) forms, which are required for a complete spermatogenesis, and are generated by alternative splicing of optional exon 6, encoding sites of proteolysis. We show that in the mouse testis, the alternative splicing of SCF is developmentally regulated. SCFs predominates in
fetal and neonatal gonads and is then replaced by SCFm in the prepubertal and adult gonads. By sequencing SCF exon 6, we show that
the flanking intronic sequences perfectly follow the gt-at rule,
suggesting that the basal splicing machinery might not be responsible
by itself for exon 6 skipping. Moreover, freshly isolated Sertoli cells
mainly express SCFm, but a switch to SCFs occurs after 48 h of
culture. We found that this change can be prevented by acidification of
the culture medium at pH 6.3 or by addition of lactate. The sustained
synthesis of SCFm at low pH was no longer observed in the presence of
cycloheximide, suggesting that SCF exon 6 skipping requires de
novo protein synthesis. Accordingly, UV cross-linking experiments
show that nuclear Sertoli cell protein(s) bind in a sequence-specific
manner to exon 6. Together, our data allow the proposal of an
integrated mechanism in which the synthesis of lactate by Sertoli cells
is used in the same time as an energetic substrate for germ cells and
as a promoter of their survival/proliferation through the production of SCFm.
INSERM U407, Laboratoire de Physiologie de la Reproduction,
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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