Study of the mouse sortilin gene: Effects of its transient silencing by RNA interference in TM4 Sertoli cells

Molecular Reproduction and Development
Jibin ZengC R Morales

Abstract

Using databases of the mouse genome in combination with a sequence deduced from a mouse sortilin cDNA originated in our laboratory, we found the sortilin gene to map to a region of chromosome 3. The mouse sortilin gene contains 19 short exons separated by introns of various sizes. The study elucidated the exon-intron boundaries. Some introns extend over more than 24 kb. In the cytoplasmic domain of the translation product, we found a dileucine motif and three other motifs known to constitute the active sorting signal of the mannose 6-phosphate receptor (M6P-R). We also tested the hypothesis that sortilin is involved in the sorting of prosaposin (SGP-1) to the lysosomes. Prosaposin was initially identified in Sertoli cells, found in large amounts in the lysosomal compartment and implicated in the degradation of residual bodies released by the spermatids during spermiation. Interestingly, the targeting of prosaposin to the lysosomes is independent of the M6P-R. This investigation demonstrated that sortilin was required for the trafficking of prosaposin to the lysosomes in TM4 cells. The requirement of sortilin was shown using a siRNA probe to block the translation of sortilin mRNA. Sortilin-deficient cells were not able to route ...Continue Reading

References

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Dec 6, 2003·The EMBO Journal·Stephane LefrancoisCarlos R Morales

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Citations

Aug 13, 2011·Experimental Cell Research·Libin Yuan, Carlos R Morales
Oct 19, 2005·The Journal of Biological Chemistry·Thomas KolterKonrad Sandhoff

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