Association of Kinesin Light Chain with Outer Dense Fibers in a Microtubule-independent Fashion

Bhullar, Bhupinder; Zhang, Ying; Junco, Albert; Oko, Richard; Hoorn, Frans A. van der

doi:10.1074/jbc.m213126200

Cited by 32 publications

(36 citation statements)

References 60 publications

(87 reference statements)

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“…However, binding partners that mediate the connection to the nucleus at the implantation fossa via the basal plate are currently not known. Among the identified ODF1-interacting proteins, none is located at a position to possibly function in sperm head-tail coupling (Shao et al 1999, Bhullar et al 2003, Zarsky et al 2003, Zhang et al 2004, Fitzgerald et al 2005. The basal plate and its intrinsic proteins are crucial when looking for the head-tail coupling apparatus.…”

Section: Discussionmentioning

confidence: 99%

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

Yang¹,

Grzmil²,

Meinhardt³

et al. 2014

Reproduction

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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.

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Section: Discussionmentioning

confidence: 99%

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

Yang¹,

Grzmil²,

Meinhardt³

et al. 2014

Reproduction

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“…Instead, a promising candidate that could be responsible for mediating the tight packaging of mitochondria and their association to the ODFs in the midpiece of the sperm tail is the kinesin light chain, KLC3. KLC3 has not only been shown to interact with ODF1 but also to associate with mitochondria in the sperm tail (4,64). Lack of its binding partner ODF1 could thus affect the tight mitochondrial association to the ODFs eventually resulting in its disturbed arrangement.…”

Section: Figmentioning

confidence: 99%

“…The scaffold of the ODF fiber may thus be structured by the two main ODF proteins, ODF1 and ODF2 (46). Other ODF1 interacting proteins are SPAG4, KLC3 (kinesin light chain 3), OIP1 (ODF1-interacting protein), and SPAG5 (4,18,52,63). SPAG4 is located in the transient manchette and associated with the axoneme in elongating spermatids and epididymal sperm.…”

mentioning

confidence: 99%

The Small Heat Shock Protein ODF1/HSPB10 Is Essential for Tight Linkage of Sperm Head to Tail and Male Fertility in Mice

Yang

Meinhardt

Zhang

et al. 2012

Molecular and Cellular Biology

131

122

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Sperm motility and hence male fertility strictly depends on proper development of the sperm tail and its tight anchorage to the head. The main protein of sperm tail outer dense fibers, ODF1/HSPB10, belongs to the family of small heat shock proteins that function as molecular chaperones. However, the impact of ODF1 on sperm tail formation and motility and on male fecundity is unknown. We therefore generated mutant mice in which the Odf1 gene was disrupted. Heterozygous mutant male mice are fertile while sperm motility is reduced, but Odf1-deficient male mice are infertile due to the detachment of the sperm head. Although headless tails are somehow motile, transmission electron microscopy revealed disturbed organization of the mitochondrial sheath, as well as of the outer dense fibers. Our results thus suggest that ODF1, besides being involved in the correct arrangement of mitochondrial sheath and outer dense fibers, is essential for rigid junction of sperm head and tail. Loss of function of ODF1, therefore, might account for some of the cases of human infertility with decapitated sperm heads. In addition, since sperm motility is already affected in heterozygous mice, impairment of ODF1 might even account for some cases of reduced fertility in male patients.

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“…Each structure is composed of a heterogeneous array of polypeptides, but relatively few of these have been identified and characterized (5)(6)(7)(8)(9). The ODF, FS, and mitochondrial sheath proteins that have been identified are conserved among various mammalian species, suggesting they perform critical functions.…”

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confidence: 99%

Proteomic Profiling of Accessory Structures from the Mouse Sperm Flagellum

Cao

Gerton²,

Moss³

2006

Molecular & Cellular Proteomics

162

148

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The flagellum of a mammalian spermatozoon consists of an axoneme surrounded in distinct regions by accessory structures known as the fibrous sheath, outer dense fibers, and the mitochondrial sheath. Although the characterization of individual proteins has provided clues about the roles of these accessory structures, a more complete understanding of flagellar function requires the identification of all the polypeptides in these assemblies. Epididymal mouse sperm were treated with SDS to dislodge sperm heads and to extract the axoneme and membranous elements. The remaining flagellar accessory structures were purified by sucrose gradient centrifugation. Analysis of proteins from these structures by two-dimensional gel electrophoresis and colloidal Coomassie Blue staining showed a highly reproducible pattern of >200 spots. Individual spots were picked, digested with trypsin, and identified by mass spectrometry and peptide microsequencing. Approximately 50 individual proteins were identified that could be assigned to five general categories: 1) proteins previously reported to localize to the accessory structures, e.g. ODF2 in the outer dense fibers, the spermspecific glyceraldehyde-3-phosphate dehydrogenase in the fibrous sheath, and glutathione peroxidase in the mitochondrial sheath, validating this proteomic approach; 2) proteins that had not been shown to localize to any accessory structure but would be predicted to be present, e.g. glycolytic enzymes; 3) proteins known to be part of the flagellum but not localized to a specific site, e.g. adenylate kinase; 4) proteins not expected to be part of the accessory structures based on their previously reported locations, e.g. tektins; and 5) unknown proteins for which no information is available to make a determination as to location. The unexpected presence of the tektins in the accessory structures of the flagellum was confirmed by both immunoblot and immunofluorescence analysis. This proteomic analysis identified a number of unexpected and novel proteins in the accessory structures of the mammalian flagellum. The mammalian sperm flagellum is a complex structure whose proper assembly and function are critical for sperm motility and subsequent fertilization of the egg. Morphologically the flagellum is characterized by three distinct regions: the midpiece, the principal piece, and the end piece. Common to these three segments is the axoneme or "motor" of the flagellum that runs the length of this structure and is composed of the typical "9 ϩ 2" array of microtubules (1, 2). In the different segments, the axoneme may be surrounded by accessory structures: the mitochondrial sheath, outer dense fibers (ODFs), 1 and/or the fibrous sheath (FS). The midpiece is proximal to the sperm head and contains nine ODFs paired with the nine peripheral doublet microtubules, forming a "9 ϩ 9 ϩ 2" pattern. The mitochondrial sheath contains all the mitochondria of the sperm and is helically arranged around the ODFs in this region. Proximal to the midpiece is the principal piece. Seven of t...

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Association of Kinesin Light Chain with Outer Dense Fibers in a Microtubule-independent Fashion

Cited by 32 publications

References 60 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

The Small Heat Shock Protein ODF1/HSPB10 Is Essential for Tight Linkage of Sperm Head to Tail and Male Fertility in Mice

Proteomic Profiling of Accessory Structures from the Mouse Sperm Flagellum

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