Haploid male germ cells—the Grand Central Station of protein transport

Abstract BACKGROUND The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility. OBJECTIVE AND RATIONALE This review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility. SEARCH METHODS Relevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis. OUTCOMES Spermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility. WIDER IMPLICATIONS A greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.

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Knockout of serine-rich single-pass membrane protein 1 (Ssmem1) causes globozoospermia and sterility in male mice†

Biology of Reproduction ◽

10.1093/biolre/ioaa040 ◽

2020 ◽

Vol 103 (2) ◽

pp. 244-253

Author(s):

Kaori Nozawa ◽

Qian Zhang ◽

Haruhiko Miyata ◽

Darius J Devlin ◽

Zhifeng Yu ◽

...

Keyword(s):

Membrane Protein ◽

Male Infertility ◽

Sperm Motility ◽

Sperm Head ◽

Specific Gene ◽

Cell Organelles ◽

Single Pass ◽

Human Male ◽

Transmission Electron ◽

Golgi Network

Abstract Globozoospermia (sperm with an abnormally round head shape) and asthenozoospermia (defective sperm motility) are known causes of male infertility in human patients. Despite many studies, the molecular details of the globozoospermia etiology are still poorly understood. Serine-rich single-pass membrane protein 1 (Ssmem1) is a conserved testis-specific gene in mammals. In this study, we generated Ssmem1 knockout (KO) mice using the CRISPR/Cas9 system, demonstrated that Ssmem1 is essential for male fertility in mice, and found that SSMEM1 protein is expressed during spermatogenesis but not in mature sperm. The sterility of the Ssmem1 KO (null) mice is associated with globozoospermia and loss of sperm motility. To decipher the mechanism causing the phenotype, we analyzed testes with transmission electron microscopy and discovered that Ssmem1-disrupted spermatids have abnormal localization of Golgi at steps eight and nine of spermatid development. Immunofluorescence analysis with anti-Golgin-97 to label the trans-Golgi network, also showed delayed movement of the Golgi to the spermatid posterior region, which causes failure of sperm head shaping, disorganization of the cell organelles, and entrapped tails in the cytoplasmic droplet. In summary, SSMEM1 is crucial for intracellular Golgi movement to ensure proper spatiotemporal formation of the sperm head that is required for fertilization. These studies and the pathway in which SSMEM1 functions have implications for human male infertility and identifying potential targets for nonhormonal contraception.

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Contracture Severity at Hospital Discharge in Children: A Burn Model System Database Study

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa169 ◽

2020 ◽

Author(s):

Miranda Yelvington ◽

Matthew Godleski ◽

Austin F Lee ◽

Jeremy Goverman ◽

Ingrid Parry ◽

...

Keyword(s):

Length Of Stay ◽

Range Of Motion ◽

Hospital Discharge ◽

Injury Severity ◽

Model System ◽

Future Research ◽

P Value ◽

Local Practices ◽

Improvement Measures ◽

Joint Motions

Abstract Contractures can complicate burn recovery. There are limited studies examining the prevalence of contractures following burns in pediatrics. This study investigates contracture outcomes by location, injury, severity, length of stay, and developmental stage. Data were obtained from the Burn Model System between 1994 and 2003. All patients younger than the age of 18 with at least one joint contracture at hospital discharge were included. Sixteen areas of impaired movement from the shoulder, elbow, wrist, hand, hip, knee, and ankle joints were examined. Analysis of variance was used to assess the association between contracture severity, burn size, and length of stay. Age groupings were evaluated for developmental patterns. A P value of less than .05 was considered statistically significant. Data from 225 patients yielded 1597 contractures (758 in the hand) with a mean of 7.1 contractures (median 4) per patient. Mean contracture severity ranged from 17% (elbow extension) to 41% (ankle plantarflexion) loss of movement. Statistically significant associations were found between active range of motion loss and burn size, length of stay, and age groupings. The data illustrate quantitative assessment of burn contractures in pediatric patients at discharge in a multicenter database. Size of injury correlates with range of motion loss for many joint motions, reflecting the anticipated morbidity of contracture for pediatric burn survivors. These results serve as a potential reference for range of motion outcomes in the pediatric burn population, which could serve as a comparison for local practices, quality improvement measures, and future research.

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Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Current Pharmaceutical Design ◽

10.2174/1381612043453261 ◽

2004 ◽

Vol 10 (5) ◽

pp. 471-500 ◽

Cited By ~ 41

Author(s):

Peter Vogt

Keyword(s):

Male Infertility ◽

Molecular Genetic ◽

Human Male

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Spinal cord injury and male infertility—a review of current literature, knowledge gaps, and future research

Translational Andrology and Urology ◽

10.21037/tau.2018.04.12 ◽

2018 ◽

Vol 7 (S3) ◽

pp. S373-S382 ◽

Cited By ~ 6

Author(s):

Ross Anderson ◽

Rachel Moses ◽

Sara Lenherr ◽

James M. Hotaling ◽

Jeremy Myers

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Male Infertility ◽

Current Literature ◽

Future Research ◽

Knowledge Gaps ◽

Cord Injury

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Signal Peptide-Dependent Protein Transport inBacillus subtilis: a Genome-Based Survey of the Secretome

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.64.3.515-547.2000 ◽

2000 ◽

Vol 64 (3) ◽

pp. 515-547 ◽

Cited By ~ 522

Author(s):

Harold Tjalsma ◽

Albert Bolhuis ◽

Jan D. H. Jongbloed ◽

Sierd Bron ◽

Jan Maarten van Dijl

Keyword(s):

Protein Secretion ◽

Molecular Mechanisms ◽

Protein Transport ◽

Transport Systems ◽

Future Research ◽

Yeast Saccharomyces Cerevisiae ◽

Transport Pathways ◽

Amino Terminal ◽

Cell Factories ◽

A Genome

SUMMARY One of the most salient features of Bacillus subtilis and related bacilli is their natural capacity to secrete a variety of proteins into their environment, frequently to high concentrations. This has led to the commercial exploitation of bacilli as major “cell factories” for secreted enzymes. The recent sequencing of the genome of B. subtilis has provided major new impulse for analysis of the molecular mechanisms underlying protein secretion by this organism. Most importantly, the genome sequence has allowed predictions about the composition of the secretome, which includes both the pathways for protein transport and the secreted proteins. The present survey of the secretome describes four distinct pathways for protein export from the cytoplasm and approximately 300 proteins with the potential to be exported. By far the largest number of exported proteins are predicted to follow the major “Sec” pathway for protein secretion. In contrast, the twin-arginine translocation “Tat” pathway, a type IV prepilin-like export pathway for competence development, and ATP-binding cassette transporters can be regarded as “special-purpose” pathways, through which only a few proteins are transported. The properties of distinct classes of amino-terminal signal peptides, directing proteins into the various protein transport pathways, as well as the major components of each pathway are discussed. The predictions and comparisons in this review pinpoint important differences as well as similarities between protein transport systems in B. subtilis and other well-studied organisms, such as Escherichia coli and the yeast Saccharomyces cerevisiae. Thus, they may serve as a lead for future research and applications.

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Germline Telomere Attrition is Associated with Human Male Infertility

Indian Journal of Genetics and Molecular Research ◽

10.21088/ijgmr.2319.4782.5216.1 ◽

2016 ◽

Vol 5 (2) ◽

pp. 37-44

Author(s):

S. Pathak ◽

◽

A.S. Multani ◽

S.H. Sohn ◽

N.J. Gupta ◽

...

Keyword(s):

Male Infertility ◽

Telomere Attrition ◽

Human Male

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Status, Distribution, and Conservation of Native Freshwater Fishes of Western North America

Status, Distribution, and Conservation of Native Freshwater Fishes of Western North America ◽

10.47886/9781888569896.ch16 ◽

2007 ◽

Keyword(s):

Conservation Biology ◽

Biological Diversity ◽

Common Species ◽

Model System ◽

Future Research ◽

Evolutionary Processes ◽

Widespread Species ◽

Key Points ◽

Management Priorities ◽

Conservation And Management

ABSTRACT The fundamental charge of conservation biology is to preserve biological diversity. Yet, efforts to accomplish this goal have focused too narrowly on reversing the slide toward extinction in already threatened or endangered species. In this review, we argue that conservation biologists and fisheries managers should broaden their vision to include efforts to preserve the ecological and evolutionary processes that ultimately give rise to new biodiversity. Our view is based upon the simple observation that biological diversity is a function of both the rate at which new taxa originate as well as the rate at which established taxa are lost to extinction. Efforts to stem extinction that fail to maintain the ecological and evolutionary processes of speciation are ultimately unsustainable. We suggest that common, widespread species are particularly important to the origin of new diversity and argue that conservation biologists should pay particular attention to the evolution of diversity within such species. We illustrate several key points to this argument using the desert minnow, Utah chub <em>Gila atraria</em>, as a model system. In particular, we show that conservation efforts in common species must focus on clearly delineating conservation unit boundaries and that particular care should be paid to unique ecological and evolutionary diversity within such species.We also show the importance of understanding and conserving the range of ecological and evolutionary interactions that are common hallmarks of abundant and widespread taxa.We conclude our review by suggesting several specific areas of future research in Utah chub that would help more clearly define conservation and management priorities in this species.

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