Cilium, an organelle with a unique proteome and organization, protruding from the cell surface, generally serves as a force generator and signaling compartment. During ciliogenesis, ciliary proteins are synthesized in cytoplasm and transported into cilia by intraflagellar transport (IFT) particles, where the inner counterparts undergo reverse trafficking. The homeostasis of IFT plays a key role in cilial structure assembly and signaling transduction. Much progress has been made on the mechanisms and functions of IFT; however, recent studies have revealed the involvement of IFT particle subunits in organogenesis and spermatogenesis. In this review, we discuss new concepts concerning the molecular functions of IFT protein IFT25 and how its interactions with other IFT particle subunits are involved in mammalian development and fertility.
Animals ; Biological Transport ; Carrier Proteins/metabolism* ; Cilia/metabolism* ; Flagella/metabolism* ; Male ; Mammals/metabolism* ; Organogenesis ; Proteins/metabolism* ; Signal Transduction

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.
Humans ; Male ; Consanguinity ; Pakistan ; Infertility, Male/metabolism* ; Semen/metabolism* ; Sperm Tail/metabolism* ; Spermatozoa/metabolism* ; Flagella/pathology* ; Mutation

AIMTo investigate the human sperm oxygen/energy consumption and zinc content in relation to motility.

METHODSIn washed spermatozoa from 67 ejaculates, the oxygen consumption was determined. Following calculation of the total oxygen consumed by the Ideal Gas Law, the energy consumption of spermatozoa was calculated. In addition, the zinc content of the sperm was determined using an atomic absorption spectrometer. The resulting data were correlated to the vitality and motility.

RESULTSThe oxygen consumption averaged 0.24 micromol/10(6) sperm x 24h, 0.28 micromol/10(6) live sperm x 24h and 0.85 micromol/10(6) live motile sperm x 24h. Further calculations revealed that sperm motility was the most energy consuming process (164.31 mJ/10(6) motile spermatozoa x 24h), while the oxygen consumption of the total spermatozoa was 46.06 mJ/10(6) spermatozoa x 24h. The correlation of the oxygen/energy consumption and zinc content with motility showed significant negative correlations (r= -0.759; P<0.0001 and r=-0.441; P<0.0001, respectively). However, when correlating sperm energy consumption with the zinc content, a significant positive relation (r=0.323; P=0.01) was observed.

CONCLUSIONPoorly motile sperm are actually wasting the available energy. Moreover, our data clearly support the "Geometric Clutch Model" of the axoneme function and demonstrate the importance of the outer dense fibers for the generation of sperm motility, especially progressive motility.

Adult ; Energy Metabolism ; physiology ; Flagella ; physiology ; Humans ; Male ; Middle Aged ; Oxygen Consumption ; Sperm Motility ; physiology ; Spermatozoa ; metabolism ; Zinc ; metabolism

Bacterial Proteins ; genetics ; metabolism ; Biofilms ; DNA-Binding Proteins ; genetics ; metabolism ; Flagella ; genetics ; metabolism ; Gene Expression Regulation, Bacterial ; Transcription Factors ; genetics ; metabolism ; Vibrio parahaemolyticus ; cytology ; genetics ; growth & development ; physiology

Salmonella causes a wide variety of diseases ranging from mild diarrhea to severe systemic infections, such as like typhoid fever, in multiple organisms, ranging from mice to humans. A lack of ptsI, which encodes the first component of phosphoenolpyruvate (PEP) : carbohydrate phosphotransferase system (PTS), is known to cause Salmonella Typhimurium attenuation; however, the mechanisms behind this have not yet been elucidated. In this study, a DNA microarray was performed to determine why the virulence of ptsI mutants is attenuated under low-oxygen conditions in which the ptsI expression is enhanced. Of 106 down-regulated genes, the most repressed were pdu and tdc genes, which are required for propanediol utilization and threonine and serine metabolism, respectively. In addition, half the flagellar genes were down-regulated in the ptsI mutant strain. Because pdu genes are induced during infection and Tdc products and flagella-mediated motility are necessary for the invasion of S. Typhimurium, the invasive ability of ptsI mutants was examined. We found that ptsI mutation reduced the ability of S. Typhimurium to invade into host cells, suggesting that reduced expression of the pdu, tdc, and flagellar genes is involved in the attenuation of ptsI mutants.
Animals ; Diarrhea ; Flagella ; Humans ; Metabolism ; Mice ; Microarray Analysis* ; Oligonucleotide Array Sequence Analysis ; Phosphoenolpyruvate ; Salmonella typhimurium* ; Salmonella* ; Serine ; Threonine ; Typhoid Fever ; Virulence

To investigate the function of STT3a gene in salt adaptation and flagellar regeneration of Dunaliella salina (D. salina), a pair of degenerate primers was designed according to conserved homologous amino acid sequences of VCVFTA and DVDYVL of STT3a from Chlamydomonas, Arabidopsis thaliana and other organisms. A cDNA sequence of 1 650 bp encoding a whole functional domain of STT3a was amplified from D. salina by RT-PCR and 3' Rapid Amplification of cDNA Ends (RACE), which shared homology with Chlamydomonas (48%), Arabidopsis thaliana (50%), Homo sapiens (46%), etc. Real-time fluorescence quantitative PCR (real-time Q-PCR) demonstrated that the STT3a mRNAs from D. salina were induced by increased concentration of NaCl, and increased to 11-fold higher by 3.5 mol/L NaCl than that by 1.5 mol/L NaCl (P < 0.01). Also, STT3a mRNA of D. salina maintained at a higher level in the process of flagellar regeneration with than without experiencing deflagellar treatment. In conclusion, the findings of this study demonstrate that the high expression of the STT3a gene enhances the capability of salt adaptation and flagellar regeneration in D. salina.
Adaptation, Physiological ; physiology ; Arabidopsis ; enzymology ; Chlamydomonas ; enzymology ; Chlorophyta ; enzymology ; genetics ; Cloning, Molecular ; Flagella ; metabolism ; Hexosyltransferases ; chemistry ; genetics ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; genetics ; metabolism ; Sodium Chloride ; pharmacology

One of the most widespread cellular organelles in nature is cilium, which is found in many unicellular and multicellular organisms. Formerly thought to be a mostly vestigial organelle, the cilium has been discovered in the past several decades to play critical motile and sensory roles involved in normal organogenesis during development. The role of cilia has also been implicated in an ever increasing array of seemingly unrelated human diseases, including blindness, kidney cysts, neural tube defects and obesity. In this article we review some of the recent developments in research on cilia, and how defects in ciliogenesis and function can give rise to developmental disorders and disease.
Abnormalities, Multiple ; pathology ; Animals ; Cerebellar Diseases ; genetics ; pathology ; Cilia ; physiology ; ultrastructure ; Flagella ; physiology ; Hedgehog Proteins ; metabolism ; Humans ; Models, Animal ; Polycystic Kidney Diseases ; pathology ; Protein Transport ; Signal Transduction ; Wnt Proteins ; metabolism