Disease relevance of ZAN

• Mutation in the zonadhesin-like domain of alpha-tectorin associated with autosomal dominant non-syndromic hearing loss [1].

High impact information on ZAN

• Finally, we observe adaptive evolution in haplotypes segregating for a frameshift mutation that was previously thought to indicate that ZAN was a potential pseudogene [2].
• Zonadhesin is a male reproductive protein localized on the sperm head, comprising many domains known to be involved in cell-cell interaction or cell adhesion [2].
• Molecular population genetics of the gene encoding the human fertilization protein zonadhesin reveals rapid adaptive evolution [2].
• Here we analyze the sequence evolution of zonadhesin, a mammalian sperm ligand that binds to the oocyte zona pellucida in a species-specific manner [3].
• Zonadhesin is the only sperm protein known to bind in a species-specific manner to the zona pellucida [4].

Biological context of ZAN

• Chromosome localization of the mouse zonadhesin gene and the human zonadhesin gene (ZAN) [5].
• During sperm maturation in the epididymis, zonadhesin dissociated from the outer acrosomal membrane and became incorporated into the forming acrosomal matrix [4].
• Zonadhesin assembly into the hamster sperm acrosomal matrix occurs by distinct targeting strategies during spermiogenesis and maturation in the epididymis [4].
• One of the changes results in a cysteine to serine (C 1057 S) mutation, in the zonadhesin domain of TECTA; this segregates with the disease haplotype on chromosome 11 and is not present in a control population [6].
• A missense mutation (C1619S) was identified in the zonadhesin-like domain [1].

Anatomical context of ZAN

• Subsequent redistribution of zonadhesin resulted in its elimination from the inner acrosomal membrane and restriction to the outer acrosomal membrane of the apical and principal segments and the contents of the posterior acrosome [4].
• In this study of hamster spermatozoa, we demonstrate that zonadhesin does not localize to the sperm surface but is instead a constituent of the acrosomal matrix [4].
• In round spermatids, zonadhesin localized specifically to the acrosomal membrane, where it appeared to be evenly distributed between the outer and inner membrane domains [4].
• These data suggest an important structural role for zonadhesin in assembly of the acrosomal matrix and further support the view that the species specificity of zona pellucida adhesion is mediated by egg-binding proteins contained within the acrosome rather than on the periacrosomal plasma membrane [4].

Associations of ZAN with chemical compounds

• The mutation results in the replacement of a cysteine in one of the repeats of the zonadhesin/Von Willebrand domain of the protein and might cause a change in the crosslinking of the polypeptide [6].

Other interactions of ZAN

• We have focussed on spermadhesins, the zonadhesin, proacrosin and the PH-20 antigen [7].

Analytical, diagnostic and therapeutic context of ZAN

• From Jaeger (1) a Masterlab bodyplethysmograph, (2) a Pneumoscreen pneumotachograph, (3) a Masterscreen CS-FRC and (4) a Masterlab CompactTransfer (the latter two measure the diffusion capacity) were compared, and from ZAN a bodyplethysmograph system encompassing spirometry, flow-volume curve and diffusion capacity measurements [8].
• Immunoelectron microscopy revealed that distinct targeting pathways during spermiogenesis and sperm maturation in the epididymis result in trafficking of zonadhesin to the acrosomal matrix [4].

References