Disease relevance of ACRV1

• A recombinant SP-10 fusion protein was produced in an Escherichia coli expression vector and used to generate a polyclonal antiserum [1].
• These data demonstrate that the carrier-free T1-SP10 synthetic peptide construct can induce high titers of neutralizing anti-HIV antibody responses and PBMC proliferative responses to HIV in primates [2].
• When combined in a trivalent inoculum, T1-SP10 peptides from HIV-1 isolates IIIB, MN, and RF evoked a high titered neutralizing antibody response to isolates IIIB, MN, and RF in goats and as well induced immune T cells to undergo blast transformation in the presence of peptides derived from gp120 of all three HIV isolates [3].
• A monoclonal antibody to human SP-10 inhibits in vitro the binding of human sperm to hamster oolemma but not to human Zona pellucida [4].
• Furthermore, we demonstrated that the oolemmal ligands of human SP-10 did not include beta(1) integrins, the most promising candidates for oocyte ligands involved in sperm-oolemma binding, based on the findings of a human sperm-cultured cell binding assay using F9 mouse embryonal carcinoma cells and F9-transformed cells lacking beta(1) integrins [4].

High impact information on ACRV1

• Antibodies to both portions of suREJ3 localize exclusively to the plasma membrane over the acrosomal vesicle [5].
• Sea urchin sperm contain a single exocytotic vesicle, the acrosomal vesicle, whose contents are exposed during the acrosome reaction [6].
• We have previously described a synthetic peptide (T1-SP10) derived from two noncontiguous regions of HTLVIIIB envelope gp120 (T1, amino acids 428-443; SP10, amino acids 303-321) that induced type-specific anti-HIV neutralizing antibodies and T cell proliferative responses against native HIV gp120 when used as a carrier-free immunogen in goats [2].
• Sera from all four animals given T1-SP10 in IFA or threonyl-MDP neutralized infection by HTLVIIIB and blocked virus-dependent cell fusion events [2].
• In previous studies, we have used antisera raised to envelope (env)-gene-encoded synthetic peptides to identify a region of (HIV) glycoprotein (gp) 120 env protein designated SP10 that contains a type-specific neutralizing determinant [3].

Chemical compound and disease context of ACRV1

• The benzamide derivative N-[1-(7-tert-Butyl-1H-indol-3-ylmethyl)-2-(4-cyclopropanecarbonyl-3-methyl-piperazin-1-yl)-2-oxo-ethyl]-4-nitro-benzamide (SP-10) reduces HIV-1 infectivity in vitro by modifying actin dynamics [7].
• Fipronil provided delayed toxicity at 21-23 degrees C with SP10 values ranging from 270 to 960 min [8].

Biological context of ACRV1

• Refinement of the localization of the gene for human intraacrosomal protein SP-10 (ACRV1) to the junction of bands q23-->q24 of chromosome 11 by nonisotopic in situ hybridization [9].
• cDNAs coding for the intra-acrosomal protein SP-10 were cloned and characterized as a first step in understanding the expression of this antigen during spermatogenesis [1].
• Interestingly, cDNA SP-10-10 has an internal 57-base pair (19 amino acids) in-frame deletion that is not present in SP-10-5, suggesting that alternative splicing generates more than one SP-10 mRNA [1].
• Recombinant SP-10 is currently being tested as a contraceptive vaccine immunogen on the basis of its tissue specificity as well as functional assays indicating that anti-SP-10 antisera inhibit sperm-egg interactions [10].
• Mapping and sequencing of the 8-kb SP-10 gene show that the SP-10 mRNA consists of exons of 119, 487, 113, and 390 bp with each exon coding for a distinct structural domain within the SP-10 protein [10].

Anatomical context of ACRV1

• After a follicular fluid-induced acrosome reaction, SP-10 was detected on the inner acrosomal membrane in the equatorial segment and was associated with hybrid vesicles [11].
• The human sperm antigen SP-10 is a testis-specific protein associated with the matrix of the acrosomal vesicle in developing spermatids and the acrosomal matrix and membranes of ejaculated sperm [9].
• Three overlapping SP-10-specific cDNAs were isolated from a human testes cDNA expression library [1].
• The human sperm antigen SP-10 has been shown to be a testis-specific, intra-acrosomal protein that is associated with the membranes and matrix of the acrosomal vesicle [12].
• A previous study, utilizing somatic cell hybrids, localized the gene for SP-10 to chromosome 11 and assigned the gene symbol ACRV1 (acrosomal vesicle protein-1) [9].

Associations of ACRV1 with chemical compounds

• After induction of the acrosome reaction with the ionophore A23187, SP-10 remained displayed on the sperm head in association with the inner acrosomal membrane and equatorial segment [13].
• In conclusion, our present data suggest that human SP-10, expressed on the equatorial region of acrosome-reacted sperm, indeed mediates sperm-oolemma binding in a beta(1) integrin-independent manner, but not sperm-zona binding [4].
• The interaction of the human acrosomal protein SP-10 with the acrosomal membranes was analyzed by the ability of Triton X-114 (TX-114) and other agents to release SP-10 from the acrosome [14].
• Sequential treatments of human sperm with various agents showed that repeated washes with TX-114 or 1.5 M NaCl had little or no effect on TX-114-resistant SP-10, whereas treatment with a chaotropic salt (150 mM sodium thiocyanate) and buffers at pH extremes (pH 2.0 and 10.0) completely released this pool of SP-10 from the acrosome [14].
• Low-temperature post-embed labeling of thin sections with wheat germ agglutinin and monoclonal antibody J18/2 show concentrations of label within the acrosomal vesicle of Strongylocentrotus purpuratus sperm, suggesting the presence of an intracellular storage site for the 210 kDa glycoprotein [15].

Regulatory relationships of ACRV1

• In co-incubation experiments, SP-10 also inhibited the CCR5-sensitive HIV-1 BaL virus replication in human peripheral blood mononuclear cells [7].

Other interactions of ACRV1

• Confocal laser scanning microscopy and immunoprecipitation studies showed that SP-10 reduced the expression of CD4 and CCR5 on the surface of the host cell [7].
• The functions of suREJ2 and suREJ3 have not been explored, but suREJ3 is exclusively localized on the plasma membrane over the sperm acrosomal vesicle and is physically associated with sea urchin polycystin-2, a known cation channel [16].
• The full-length open reading frames for hSP-10 and bSP-10 were placed under the inducible T7 bacteriophage RNA polymerase/promoter system [17].
• Using purified preparations of the previously described intra-acrosomal molecules acrosin and sperminogen in the pig, we observed that the MHS-10 monoclonal antibody did not react with these proteins, indicating SP-10 is distinct from these known acrosomal components [18].
• Immature spermatids and white blood cells in semen were identified by immunostaining with monoclonal antibodies to the human intra-acrosomal antigen SP-10 and the ubiquitous white cell CD-45 antigen, respectively [19].

Analytical, diagnostic and therapeutic context of ACRV1

• This antiserum stained the acrosomal cap in situ and reacted with a similar set of peptides on Western blots as did a monoclonal antibody to SP-10 [1].
• Differential diagnosis of immature germ cells in semen utilizing monoclonal antibody MHS-10 to the intra-acrosomal antigen SP-10 [20].
• Further, Northern analysis and immunohistochemistry of mouse testis showed the presence of TDP-43 in cell-types where the SP-10 gene remains repressed [21].
• Immunofluorescence showed that SP-10 was not associated with the surface of acrosome-intact, ejaculated sperm [13].
• N-terminal sequence analysis of OMC32 indicated a structural relationship to the SP-10 polypeptide family of human and baboon spermatozoa [22].

References