The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis

Akhmanova, Anna; Mausset-Bonnefont, Anne-Laure; Cappellen, Wiggert van; Keijzer, Nanda; Hoogenraad, Casper C.; Степанова, Т. Ф.; Drabek, Ksenija; Wees, Jacqueline van der; Mommaas, Mieke; Onderwater, J. J. M.; Meulen, H. van der; Tanenbaum, Marvin E.; Medema, René H.; Hoogerbrugge, Jos W.; Vreeburg, J. T. M.; Uringa, Evert-Jan; Grootegoed, J. Anton; Grosveld, Frank; Galjart, Niels

doi:10.1101/gad.344505

Cited by 103 publications

(100 citation statements)

References 37 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CLIP-170 is a microtubule plus-end-tracking protein that is associated with the spermatid manchette. Male mice carrying homozygous knockout of CLIP-170 are subfertile and produce sperm with abnormal heads [19]. Our finding suggests that SEPT7 may contribute to the formation of the perinuclear ring of the manchette.…”

Section: Discussionmentioning

confidence: 58%

The expression pattern of SEPT7 correlates with sperm morphology

Chao

Lin

Kuo

et al. 2010

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose To investigate the expression pattern of the SEPT7 protein during spermatogenesis and its potential role in sperm function. Methods We first investigated the expression pattern of SEPT7 during different steps of mouse spermiogenesis using an immunofluorescence assay (IFA). IFA was also applied to study the expression pattern of SEPT7 in human ejaculated spermatozoa. Nine fertile men with normal semen parameters were used as the control group, and 21 infertile men with asthenozoospermia were recruited as the patient group. We assessed the frequency of the SEPT7 signal in the various morphological subgroups. Results In humans, the frequency of a defective SEPT7 signal was significantly increased in men with asthenozoospermia. The absence of a SEPT7 signal was more prevalent in sperm containing morphological defects of various types. Conclusions The expression pattern of SEPT7 suggested that this protein may be involved in the regulation of subcellular-compartment formation during spermiogenesis in the mouse. The absence of a SEPT7 signal correlated with multiple sperm defects.

show abstract

Section: Discussionmentioning

confidence: 58%

The expression pattern of SEPT7 correlates with sperm morphology

Chao

Lin

Kuo

et al. 2010

J Assist Reprod Genet

View full text Add to dashboard Cite

show abstract

“…5C). This finding is common for most, if not all, of the proteins that ultimately become sperm flagellar structural proteins, because the manchette, a microtubule-enriched perinuclear structure present exclusively in step 9-14 spermatids, plays a pivotal role in orchestrating the final assembly of functional spermatozoa, not only by providing the physical forces for shaping the sperm head, but also by serving as a "conveyer belt" that mediates the efficient transportation and processing of proteins required for sperm flagellar assembly (28)(29)(30)(31)(32)(33).…”

Section: Significancementioning

confidence: 99%

Spata6 is required for normal assembly of the sperm connecting piece and tight head–tail conjunction

Yuan

Stratton

Bao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

127

View full text Add to dashboard Cite

"Pinhead sperm," or "acephalic sperm," a type of human teratozoospermia, refers to the condition in which ejaculate contains mostly sperm flagella without heads. Family clustering and homogeneity of this syndrome suggests a genetic basis, but the causative genes remain largely unknown. Here we report that Spata6, an evolutionarily conserved testis-specific gene, encodes a protein required for formation of the segmented columns and the capitulum, two major structures of the sperm connecting piece essential for linking the developing flagellum to the head during late spermiogenesis. Inactivation of Spata6 in mice leads to acephalic spermatozoa and male sterility. Our proteomic analyses reveal that SPATA6 is involved in myosin-based microfilament transport through interaction with myosin subunits (e.g., MYL6).M ale gametes-spermatozoa-are produced in the testis through a process termed spermatogenesis, which can be divided into three phases: mitotic, meiotic, and haploid (1). In the mitotic phase, spermatogonial stem cells proliferate and differentiate into spermatogonia, which subsequently enter the meiotic phase and become spermatocytes. Spermatocytes undergo crossover, followed by two consecutive meiotic cell divisions to produce haploid spermatids. Spermatids then undergo a multistep differentiation process, also called spermiogenesis, to form spermatozoa. Severe disruptions in either the mitotic or the meiotic phase tend to cause azoospermia, whereas spermiogenic defects often lead to reduced sperm counts, aberrant sperm motility, and deformed spermatozoa, a condition termed oligoasthenoteratozoospermia (OAT) in humans (2, 3).OAT accounts for a significant proportion of male idiopathic infertility cases (2, 4). Numerous cases of acephalic spermatozoa have been reported in teratozoospermic patients (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In these patients, the major anomaly lies in headless spermatozoa in the ejaculate, and the headless spermatozoa were initially called "pinhead sperm" because the investigators mistakenly regarded the retained cytoplasmic droplets, which are usually attached to the midprincipal piece junction of the flagella, as the heads of reduced size (8,13,14). Extensive ultrastructral studies on humans and animals with acephalic spermatozoa suggest that this condition results from defects in formation of the connecting piece of spermatozoa during late spermiogenesis, including failure for the proximal centrioles to attach normally to the caudal portion of the sperm nuclei, leading to abnormal head-midpiece alignment, or a nuclear defect that interferes with formation of the implantation fossa, the normal lodging site for the sperm proximal centriole (16). Aberrant formation of the connecting piece leads to independent development of the sperm heads and flagella, and eventually these structures become separated within the seminiferous tubules or during their transition through the seminal tract as a consequence of increased instability of the head-midpiece junction (16,18)....

show abstract

“…Loss of CLIP1 results in subfertility in male mice because of abnormal sperm head shape. 8 Putative cognitive impairments have not yet been studied in the Clip1 knockout mice. CLIP1 was also shown to be involved in the maintenance of a normal neuromuscular phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…We note that also in mouse CLIP2 migrates at a higher position than expected. For a comparable western blot analysis of CLIP2 in mouse fibroblasts, please see Figure 2c in Akhmanova et al 8 Normalization was done with b-actin antibody.…”

Section: Discussionmentioning

confidence: 99%

“…In non-neuronal cells, it contributes to kinetochore-MT attachments during mitosis, 6 and is an anti-catastrophe factor in mammalian cells in interphase. 7 Moreover, it has been shown to have an important role in spermatogenesis, 8 as well as in neuronal development. 9 CLIP1 and its relative CLIP2 appear to regulate neuronal polarization through MTs and growth cone dynamics.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability

Larti¹,

Kahrizi²,

Musante³

et al. 2014

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score ¼ 3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID.

show abstract

The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis

Cited by 103 publications

References 37 publications

The expression pattern of SEPT7 correlates with sperm morphology

The expression pattern of SEPT7 correlates with sperm morphology

Spata6 is required for normal assembly of the sperm connecting piece and tight head–tail conjunction

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability

Contact Info

Product

Resources

About