TEX101, a glycoprotein essential for sperm fertility, is required for stable expression of Ly6k on testicular germ cells

Abstract

TEX101, a germ cell-specific glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein, is associated with Ly6k during spermatogenesis in testis. Although both Tex101−/− and Ly6k−/− mice can produce morphologically intact spermatozoa, both knockout mice show an infertile phenotype due to a disorder of spermatozoa to migrate into the oviduct. Since Ly6k specifically interacts with TEX101, complex formation of TEX101/Ly6k appears to be potentially important for functional sperm production. This study evaluated the fate of Ly6k in the presence or absence of TEX101 to explore the molecular interaction of both GPI-anchored proteins in seminiferous tubules. The present study showed that: 1) Although Ly6k mRNA was detected, the protein was present at very low levels in mature testes of Tex101−/− mice, 2) Ly6k mRNA level was within the normal range in Tex101−/− mice, 3) Ly6k mRNA was translated into a polypeptide in the testes of Tex101+/+ and Tex101−/− mice, and 4) TEX101, as well as Ly6k, are co-factors that affect to molecular expression. These results indicate that both TEX101 and Ly6k contribute to the post-translational counterpart protein expression at the cell membrane. This mechanism may be important in maintaining the production of fertile spermatozoa during spermatogenesis.

An update of the regulatory factors of sperm migration from the uterus into the oviduct by genetically manipulated mice

“…This finding implies the existence of a significant factor (“Protein Y”) other than ADAM3 on the surface of mammalian sperm, and this “Protein Y” is specifically regulated by LY6K to participate in sperm migration (Figure ). Additionally, TEX101 is essential for the stable expression of LY6K in testicular germ cells, but the expression of TEX101 does not depend on LY6K (Endo et al, ). Therefore, the lost of LY6K causes “Protein Y” to disappear in Tex101 ‐null mice, whereas TEX101 is still expressed normally and is responsible for subsequent ADAM3 maturation in Ly6k ‐deficient mice.…”

“…Since LY6K specifically interacts with TEX101, the formation of the TEX101/LY6K complex may potentially be important for functional sperm production (Yoshitake et al, 2008). Both TEX101 and LY6K mutually contribute to the expression of their counterpart proteins on the cell membrane (Endo et al, 2016). Intriguingly, previous studies have revealed that the transient interaction of the TEX101/LY6K complex with ADAM3 is a critical step for ADAM3 F I G U R E 5 Models for the role of TPST-2 and tyrosine O-sulfation in ADAM expression on the sperm surface.…”

“…Additionally, TEX101 is essential for the stable expression of LY6K in testicular germ cells, but the expression of TEX101 does not depend on LY6K (Endo et al, 2016). Therefore, the lost of LY6K causes "Protein Y" to disappear in Tex101-null mice, whereas TEX101 is still expressed normally and is responsible for subsequent ADAM3 maturation in Ly6k-deficient mice.…”

The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

“…Interestingly, in contrast to previously known gene knockout mouse lines, Ly6k -null spermatozoa had no aberrant expression and distribution of ADAM3. 120, 121, 122 On the other hand, LY6K is present in Clgn , Calr3 and Pdilt mutant mouse lines, suggesting that LY6K may be a novel, ultimately essential, factor independent from the ADAM3 pathway for sperm migrating and/or fertilizing ability.…”

Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection of Its Disrupting Antibodies

“…Similarly to other testisspecific proteins involved in PPIs, TEX101 is exclusively expressed on the surface of testicular germ cells (32) and was suggested to be a cell-surface chaperone involved in trafficking and maturation of numerous cell surface proteins essential for fertilization in mice (7,33). With four TEX101-regulated proteins (ADAM3-6) previously discovered in mice (7,34), three correspond to pseudogenes in humans, while ADAM4 gene is not present in the human genome.…”