Limits...
LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.

Liu Y, DeBoer K, de Kretser DM, O'Donnell L, O'Connor AE, Merriner DJ, Okuda H, Whittle B, Jans DA, Efthymiadis A, McLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O'Bryan MK - PLoS Genet. (2015)

Bottom Line: The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT).Manchette dysfunction leads to abnormal sperm head shaping.Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.

ABSTRACT
Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.

Show MeSH

Related in: MedlinePlus

Manchette structure in LrgukWT/WT and LrgukKaos/Kaos elongating spermatids.α-tubulin staining (green) of manchette microtubules in elongating spermatids from LrgukWT/WT(A) and LrgukKaos/Kaos mice (B) are shown in progressive steps during head elongation. Nuclei were stained with DAPI (blue). The scale bar = 5 μm. Please see S3 Fig. for negative control images.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4363142&req=5

pgen.1005090.g005: Manchette structure in LrgukWT/WT and LrgukKaos/Kaos elongating spermatids.α-tubulin staining (green) of manchette microtubules in elongating spermatids from LrgukWT/WT(A) and LrgukKaos/Kaos mice (B) are shown in progressive steps during head elongation. Nuclei were stained with DAPI (blue). The scale bar = 5 μm. Please see S3 Fig. for negative control images.

Mentions: LrgukKaos/Kaos spermatids also contained abnormal manchettes (S2 Fig., Fig. 4D and Fig. 5). The manchette is a grass skirt-like structure that encircles the elongating spermatid nucleus. As indicated above, it has a role in both nuclear shaping and protein transport into the growing sperm tail via a process called intra-manchette transport [13,18]. In normal spermatids, the manchette contains a series of parallel microtubule bundles that extend from a perinuclear ring and lie in close proximity to, and are parallel with, the nuclear membrane into the distal cytoplasm (Fig. 4C and Fig. 5). An analysis of elongating LrgukKaos/Kaos spermatids, using α-tubulin as a microtubule marker, revealed that the manchettes formed at the correct time and that the perinuclear ring began to move caudally along the sperm head during spermiogenesis (Fig. 5). The microtubule bundles of the manchette skirt were, however, unevenly distributed and had a ‘raggedy’ appearance compared to wild type cells. Further, and based on both the light and electron microscopic images the distal movement of the manchette along the nucleus that normally occurs during elongation was also abnormal in LrgukKaos/Kaos spermatids (Fig. 5, S3 Fig.). In contrast the perinuclear ring of the manchette continued to constrict, as it would normally, thus leading to nuclear distortion (Fig. 4C, Fig. 5 and S2 Fig.).


LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.

Liu Y, DeBoer K, de Kretser DM, O'Donnell L, O'Connor AE, Merriner DJ, Okuda H, Whittle B, Jans DA, Efthymiadis A, McLachlan RI, Ormandy CJ, Goodnow CC, Jamsai D, O'Bryan MK - PLoS Genet. (2015)

Manchette structure in LrgukWT/WT and LrgukKaos/Kaos elongating spermatids.α-tubulin staining (green) of manchette microtubules in elongating spermatids from LrgukWT/WT(A) and LrgukKaos/Kaos mice (B) are shown in progressive steps during head elongation. Nuclei were stained with DAPI (blue). The scale bar = 5 μm. Please see S3 Fig. for negative control images.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363142&req=5

pgen.1005090.g005: Manchette structure in LrgukWT/WT and LrgukKaos/Kaos elongating spermatids.α-tubulin staining (green) of manchette microtubules in elongating spermatids from LrgukWT/WT(A) and LrgukKaos/Kaos mice (B) are shown in progressive steps during head elongation. Nuclei were stained with DAPI (blue). The scale bar = 5 μm. Please see S3 Fig. for negative control images.
Mentions: LrgukKaos/Kaos spermatids also contained abnormal manchettes (S2 Fig., Fig. 4D and Fig. 5). The manchette is a grass skirt-like structure that encircles the elongating spermatid nucleus. As indicated above, it has a role in both nuclear shaping and protein transport into the growing sperm tail via a process called intra-manchette transport [13,18]. In normal spermatids, the manchette contains a series of parallel microtubule bundles that extend from a perinuclear ring and lie in close proximity to, and are parallel with, the nuclear membrane into the distal cytoplasm (Fig. 4C and Fig. 5). An analysis of elongating LrgukKaos/Kaos spermatids, using α-tubulin as a microtubule marker, revealed that the manchettes formed at the correct time and that the perinuclear ring began to move caudally along the sperm head during spermiogenesis (Fig. 5). The microtubule bundles of the manchette skirt were, however, unevenly distributed and had a ‘raggedy’ appearance compared to wild type cells. Further, and based on both the light and electron microscopic images the distal movement of the manchette along the nucleus that normally occurs during elongation was also abnormal in LrgukKaos/Kaos spermatids (Fig. 5, S3 Fig.). In contrast the perinuclear ring of the manchette continued to constrict, as it would normally, thus leading to nuclear distortion (Fig. 4C, Fig. 5 and S2 Fig.).

Bottom Line: The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT).Manchette dysfunction leads to abnormal sperm head shaping.Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.

ABSTRACT
Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.

Show MeSH
Related in: MedlinePlus