Disease relevance of Hrb

• CONCLUSIONS: These aberrations, in Hrb(-/-) mouse spermatids and sperm, are reminiscent of human familial male infertility with oligoasthenoteratozoospermia syndrome [1].
• Binding studies using an eight-residue NPF-containing peptide derived from RAB, the cellular cofactor of the HIV Rev protein, show a hydrophobic peptide-binding pocket formed by conserved tryptophan and leucine residues [2].

High impact information on Hrb

• In wild-type spermatids, Hrb is associated with the cytosolic surface of proacrosomic transport vesicles that fuse to create a single large acrosomic vesicle at step 3 of spermiogenesis [3].
• Lack of acrosome formation in Hrb-deficient mice [3].
• Here we report that male mice with a null mutation in Hrb are infertile and display round-headed spermatozoa that lack an acrosome [3].
• We conclude that Hrb is required for docking and/or fusion of proacrosomic vesicles during acrosome biogenesis [3].
• Monoclonal antibody Rip specifically recognizes 2',3'-cyclic nucleotide 3'-phosphodiesterase in oligodendrocytes [4].

Biological context of Hrb

• RESULTS: Hrb(-/-) male mice exhibited multiple anomalies during meiosis and spermiogenesis that produced developmentally impaired sperm with unshaped or deformed nuclei, loss in cell polarity, intracellular flagellar coiling, multinucleation, supernumerary centrioles and multiflagellation [1].
• METHODS: Hrb(-/-) testes, epididymides, spermatids and sperm were analyzed by histology and electron microscopy [1].
• The human genome is predicted to contain 60 RAB genes, suggesting that future work could reveal further links between Rab dysfunction and disease [5].
• It contains characteristic signatures of RAB proteins: 4 GTP binding domains, 5 RAB specific domains, 3 RAB subfamily-specific domains, and a prenylation site. lmlrab is a single copy gene, transcribed as a 3.5 kb mRNA, highly conserved in Leishmania species, and encodes a protein doublet of approximately 75 kDa [6].

Anatomical context of Hrb

• Here we report that the lack of an acrosome in Hrb mutant spermatids does not prevent the development of the acroplaxome [7].
• We also show that the actin-based motor protein myosin Va and its receptor, Rab27a/b, known to be involved in vesicle transport, are present in the Golgi and Golgi-derived proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids [7].
• The Hrb(-/-) sperm exhibited variation in head size and shape, disarranged cellular organelles, nuclear and cytoplasmic vacuolization, mitochondrial loss or scattering and no forward motility [1].
• The antigen recognized with monoclonal antibody (mAb) Rip (Rip-antigen) has been long used as a marker of oligodendrocytes and myelin sheaths [4].

Other interactions of Hrb

• In the Hrb mutant, myosin-Va-bound proacrosome vesicles tether to the acroplaxome, where they flatten and form a flat sac, designated pseudoacrosome [7].
• Our findings support the interpretation that the acroplaxome provides a focal point for myosin-Va/ Rab27a/b-driven proacrosomal vesicles to accumulate, coalesce, and form an acrosome in wild-type spermatids and a pseudoacrosome in Hrb mutant spermatids [7].
• Hrb, a protein that contains several NPF motifs (Asn-Pro-Phe) and interacts with proteins with Eps15 homology domains, is regarded as critical for the docking and/or fusion of Golgi-derived proacrosomal vesicles [7].

Analytical, diagnostic and therapeutic context of Hrb

• Rabbit anti-bone marrow serum (RAB) had no effect on the mixed lymphocyte reaction (MLR) nor on cell-mediated lysis (CML) [8].
• As this antibody worked very well on immunocytochemistry and immunohistochemistry, Rip-antigen was immunopurified with mAb-Rip from the differentiated CG-4 cells [4].

References