cDNA Cloning and Characterization of a Human Sperm Antigen (SPAG6) with Homology to the Product of the Chlamydomonas PF16 Locus

Neilson, Lorna; Schneider, P A; Deerlin, Peter G. Van; Kiriakidou, Marianthi; Driscoll, Deborah A.; Pellegrini, Maria; Millinder, Shawn; Yamamoto, Karen K.; French, Cynthia K.; Strauss, Jerome F.

doi:10.1006/geno.1999.5914

Cited by 67 publications

(66 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Scale bars in electron micrographs are 50 nm. the homologue of the Chlamydomonas PF16 locus encoding a protein of the central apparatus of the axoneme (Neilson et al 1999, Sapiro et al 2000, 2002. Easy sperm decapitation was also reported in mice with Oaz-t (Oaz3) deficiency, the testis-specific ornithine decarboxylase antizyme, presumably by affecting the local concentration of polyamines (Tokuhiro et al 2009).…”

Section: Discussionmentioning

confidence: 97%

Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage

Yang¹,

Grzmil²,

Meinhardt³

et al. 2014

Reproduction

View full text Add to dashboard Cite

The small heat shock protein ODF1/HSPB10 is essential for male fertility in mice. Targeted deletion of Odf1 resulted in acephalic sperm in homozygous mice of mixed background (C57BL/6J//129/Sv), whereas heterozygous animals are fully fertile. To further elucidate the function of ODF1, we generated incipient congenic mice with targeted deletion of Odf1 by successive backcrossing on the 129/Sv background. We observed that fecundity of heterozygous Odf1 C/K male mice was severely reduced over backcross generations. However, neither aberrant sperm parameters nor sperm anomalies could be observed. Ultra-structural analyses of sperm from incipient congenic heterozygous Odf1 C/K males of backcross generation N7 revealed no obvious pathological findings. However, we observed an enlargement of the distance between nuclear membrane and capitulum, indicating a weakening of the sperm head-to-tail coupling. Severe male subfertility provoked by haplo-deficiency of ODF1 is therefore most probably caused by impaired head-to-tail coupling that eventually might induce sperm decapitation on the specific conditions of in vivo fertilisation. As subfertility in haplo-deficient ODF1 male mice could not be diagnosed by semen analysis, it seems to be a paradigm for unexplained infertility that is a frequent diagnosis for male fertility impairment in humans.

show abstract

Section: Discussionmentioning

confidence: 97%

Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage

Yang¹,

Grzmil²,

Meinhardt³

et al. 2014

Reproduction

View full text Add to dashboard Cite

show abstract

“…For example, several sperm-or testisspecific proteins were identified, including an AKAP-associated sperm protein (30), SPAG 6, and Sp17. SPAG6 demonstrates 85% similarity to the Chlamydomonas protein pf16, which localizes to the flagellar central pair microtubules (31), whereas Sp17 has been localized to both the acrosomal region and throughout the sperm tail. Proteins from other tissues that contain axonemal structures were also identified, including the retinitis pigmentosa protein, RP1, and a brainspecific protein.…”

Section: Discussionmentioning

confidence: 99%

A Proteomic Analysis of Human Cilia

Ostrowski

Blackburn

Radde

et al. 2002

Molecular & Cellular Proteomics

408

147

View full text Add to dashboard Cite

Cilia play an essential role in protecting the respiratory tract by providing the force necessary for mucociliary clearance. Although the major structural components of human cilia have been described, a complete understanding of cilia function and regulation will require identification and characterization of all ciliary components. Estimates from studies of Chlamydomonas flagella predict that an axoneme contains > 250 proteins. To identify all the components of human cilia, we have begun a comprehensive proteomic analysis of isolated ciliary axon

show abstract

Section: Composition and Structure Of Central Pair Projectionsmentioning

confidence: 99%

“…Additional sequence information concerning the human cDNA will be needed to determine whether this is the human version of the PF6 gene; however, its expression in the testis is consistent with a potential flagellar function. Interestingly, recent studies have demonstrated that several of the central pair polypeptides first characterized in Chlamydomonas have closely related (i.e., 60 -70% identity) vertebrate homologues Lefebvre, 1996, 1997;Neilson et al, 1999;Sapiro et al, 2000).The large size of the PF6 protein (Ͼ238 kDa) and its sedimentation characteristics on sucrose density gradients (ϳ12.6S) suggest that the PF6 polypeptide may serve as a molecular scaffold for the assembly of components associated with the 1a projection on the C1 microtubule. The pf6 mutations result in the absence of the C1-1a projection (Figures 1 and 2) and the loss of two or more polypeptides that appear to cosediment with the PF6 protein ( Figure 9B).…”

mentioning

confidence: 99%

TheChlamydomonas PF6Locus Encodes a Large Alanine/Proline-Rich Polypeptide That Is Required for Assembly of a Central Pair Projection and Regulates Flagellar Motility

Rupp

O’Toole

Porter

2001

MBoC

113

View full text Add to dashboard Cite

Efficient motility of the eukaryotic flagellum requires precise temporal and spatial control of its constituent dynein motors. The central pair and its associated structures have been implicated as important members of a signal transduction cascade that ultimately regulates dynein arm activity. To identify central pair components involved in this process, we characterized a Chlamydomonas motility mutant (pf6-2) obtained by insertional mutagenesis. pf6-2 flagella twitch ineffectively and lack the 1a projection on the C1 microtubule of the central pair. Transformation with constructs containing a full-length, wild-type copy of the PF6 gene rescues the functional, structural, and biochemical defects associated with the pf6 mutation. Sequence analysis indicates that the PF6 gene encodes a large polypeptide that contains numerous alanine-rich, proline-rich, and basic domains and has limited homology to an expressed sequence tag derived from a human testis cDNA library. Biochemical analysis of an epitope-tagged PF6 construct demonstrates that the PF6 polypeptide is an axonemal component that cosediments at 12.6S with several other polypeptides. The PF6 protein appears to be an essential component required for assembly of some of these polypeptides into the C1-1a projection. INTRODUCTIONCilia and flagella are highly conserved structures found on diverse cell types, ranging from single-cell protozoa to multicellular tissues in humans, where they function to propel cells through a fluid environment or to transport fluid across a cell surface. Motile cilia are also found in the embryonic node (Sulik et al., 1994; Bellomo et al., 1996), where their motility appears to be critical for establishing the morphogenetic gradient that determines the left-right body axis in mammals (Nonaka et al., 1998). Defects in the assembly or activity of cilia and flagella result in a variety of abnormalities, including defects in left-right axis asymmetry, infertility, and respiratory disease (Afzelius et al., 1975; Afzelius, 1995;Supp et al., 1999). Most motile cilia and flagella contain an axoneme that consists of nine outer doublet microtubules surrounding two central singlet microtubules. The outer doublets contain binding sites for the inner and outer dynein arms, the molecular motors that power axoneme motility (reviewed by Porter, 1996;King, 2000). The dynein arms on one outer doublet interact transiently with the adjacent doublet to generate the force for interdoublet microtubule sliding. Other structures within the axoneme constrain and coordinate the activity of the multiple dynein motors and thereby convert microtubule sliding into flagellar bending.Both structural and genetic evidence indicate that the central pair microtubules and radial spokes play an important role in coordinating dynein activity. The two central pair microtubules are structurally asymmetric, and in several organisms, this apparatus has been shown to undergo clockwise rotation at a rate of approximately one turn per beat (reviewed by Omoto et al., 1999). Thes...

show abstract

cDNA Cloning and Characterization of a Human Sperm Antigen (SPAG6) with Homology to the Product of the Chlamydomonas PF16 Locus

Cited by 67 publications

References 23 publications

Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage

Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage

A Proteomic Analysis of Human Cilia

TheChlamydomonas PF6Locus Encodes a Large Alanine/Proline-Rich Polypeptide That Is Required for Assembly of a Central Pair Projection and Regulates Flagellar Motility

Contact Info

Product

Resources

About