The solute carrier family 4 (SLC4) includes 10 members (SLC4A1-5, SLC4A7-11), which are expressed in multiple tissues in the human body. The SLC4 family members differ in their substrate dependence, charge transport stoichiometry and tissue expression. Their common function is responsible for the transmembrane exchange of multiple ions, which is involved in many important physiological processes, such as erythrocyte CO₂ transport and the regulation of cell volume and intracellular pH. In recent years, many studies have focused on the role of SLC4 family members in the occurrence of human diseases. When SLC4 family members have gene mutations, a series of functional disorders will occur in the body, leading to the occurrence of some diseases. This review summarizes the recent progress about the structures, functions and disease correlation of SLC4 members, in order to provide clues for the prevention and treatment of related human diseases.
Humans ; Mutation ; SLC4A Proteins/physiology*

OBJECTIVEIn order to find the new varieties with different horticultural characters, and investigate the mutation effects of seeds of Dioscorea zingerbrensis.

METHODThe seeds were carried by a satellite into space and recovered. The space mutation effect on the germination, seedling growth, chromosomes and rhizome diosgenin content of SP, populations of D. zingerbrensis were investigated.

RESULTStimulated by space environment, the seed possessed the fast germinating characteristics. Germination rate showed no change. It was also found that a few plants were aneuploid or tetraploid. Fresh rhizome weight and rhizome diosgenin content in the second year plant were remarkably higher than those of the control. However, the increasing of third year plant was slow down, and rhizome diosgenin content in the third year plant declined simultaneously.

CONCLUSIONThe space environment showed stimulating effects on seed germination, fresh rhizome weight and rhizome diosgenin content.

Dioscorea ; chemistry ; genetics ; physiology ; Extraterrestrial Environment ; Germination ; Mutation ; Plant Extracts ; chemistry ; Seedlings ; chemistry ; genetics ; physiology

Vesicle-mediated transport of proteins is a highly regulated, multi-step process. When the vesicle is approaching its target membrane compartment, many factors are required to provide specificity and tethering between the incoming vesicle and the target membrane, before vesicle fusion can occur. Tethering factors, which include multisubunit complexes, coiled-coil proteins, with the help of small GTPases, provide the initial interaction between the vesicle and its target membrane. Of the multisubunit tethering factors, the transport protein particle (TRAPP) complexes function in a number of trafficking steps, including endoplasmic reticulum (ER)-to-Golgi transport, intra- and post-Golgi traffic and autophagosome formation. In this review, we summarize the updated progress in structure and function of TRAPP complexes as well as human diseases caused by genetic mutations in TRAPP.
Animals ; Endoplasmic Reticulum ; pathology ; physiology ; Golgi Apparatus ; pathology ; physiology ; Humans ; Mutation ; Protein Transport ; Vesicular Transport Proteins ; genetics ; physiology

Androgens, the male sex hormones, play an essential role in male sexual differentiation and development. However, the influence of these sex hormones extends beyond their roles in sexual differentiation and development. In many animal species, sex hormones have been shown to be essential for sexual differentiation of the brain during development and for maintaining sexually dimorphic behavior throughout life. The principals of sex determination in humans have been demonstrated to be similar to other mammals. However, the hormonal influence on sexual dimorphic differences in the nervous system in humans, sex differences in behaviors, and its correlations with those of other mammals is still an emerging field. In this review, the roles of androgens in gender and cognitive function are discussed with the emphasis on subjects with androgen action defects including complete androgen insensitivity due to androgen receptor mutations and 5alpha-reductase-2 deficiency syndromes due to 5alpha-reductase-2 gene mutations. The issue of the complex interaction of nature versus nurture is addressed.
Androgens ; physiology ; Cholestenone 5 alpha-Reductase ; deficiency ; genetics ; Cognition ; physiology ; Humans ; Male ; Mutation ; Sex Characteristics ; Sexual Behavior ; physiology ; Syndrome

The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididymal secretory proteins with spermatozoa in the lumen, very little is known regarding how the complex epididymal milieu as a whole is maintained, including mechanisms to prevent or control proteins that may not stay in their native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely that control/surveillance mechanisms exist within the epididymis to protect against this process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mechanisms in the epididymis, we used the cystatin family of cysteine protease inhibitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both proteins have inherent properties to aggregate and form amyloid. In this chapter, we present a brief summary of protein aggregation by the amyloid pathway based on what is known from other organ systems and describe quality control mechanisms that exist intracellularly to control protein misfolding and aggregation. We then present a summary of our studies of cystatin-related epididymal spermatogenic (CRES) oligomerization within the epididymal lumen, including studies suggesting that transglutaminase cross-linking may be one mechanism of extracellular quality control within the epididymis.
Amino Acid Substitution ; Amyloid ; physiology ; standards ; Cystatin C ; Cystatins ; genetics ; Dimerization ; Epididymis ; physiology ; Humans ; Male ; Mutation ; Protein Folding ; Proteins ; standards ; Quality Control ; Sperm Maturation ; physiology ; Transglutaminases ; physiology

Neuroligins (NLs) are postsynaptic membrane proteins expressed in the brain and mediate synaptogenesis. Neuroligin family proteins can specifically induce either excitatory or inhibitory synapses. Deletions or point mutations in neuroligin genes are found in patients with autism spectrum disorders (ASD) or mental retardations. The dysfunctions of these mutations have been tested in multiple neuroligin mouse models. In most of the models, including the human autism-linked NL3 and NL4 mutation mice, there are social interaction defects, memory impairment and repetitive behaviors. Researchers also found the excitatory/inhibitory synapse ratio altered in those mice, as well as receptor subunit composition. However, inconsistencies and debates also exist between different research approaches. In this review, we summarize the neuroligin mouse models currently available, examine the detailed alterations detected in those mice and compare the differences within different mouse models or different investigation methods, to obtain an overall picture of the current progress on neuroligin mouse models.
Animals ; Autistic Disorder ; physiopathology ; Brain ; physiopathology ; Cell Adhesion Molecules, Neuronal ; physiology ; Disease Models, Animal ; Humans ; Membrane Proteins ; physiology ; Mice ; Mutation ; Nerve Tissue Proteins ; physiology ; Synapses ; physiology

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also plays an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one of the mitosis-specific phosphorylation residues (i.e., Thr-622). However, the phosphorylation events at the remaining mitotic phosphorylation sites of TMAP have not been fully characterized in detail. Here, we report on generation and characterization of phosphorylated Thr-578- and phosphorylated Thr-596-specific antibodies. Using the antibodies, we show that phosphorylation of TMAP at Thr-578 and Thr-596 indeed occurs specifically during mitosis. Immunofluorescent staining using the antibodies shows that these residues become phosphorylated starting at prophase and then become rapidly dephosphorylated soon after initiation of anaphase. Subtle differences in the kinetics of phosphorylation between Thr-578 and Thr-596 imply that they may be under different mechanisms of phosphorylation during mitosis. Unlike the phosphorylation-deficient mutant form for Thr-622, the mutant in which both Thr-578 and Thr-596 had been mutated to alanines did not induce significant delay in progression of mitosis. These results show that the majority of mitosis-specific phosphorylation of TMAP is limited to pre-anaphase stages and suggest that the multiple phosphorylation may not act in concert but serve diverse functions.
Amino Acid Substitution ; Antibodies, Monoclonal/chemistry ; Cytoskeletal Proteins/genetics/*metabolism ; Hela Cells ; Humans ; Kinetics ; Mitosis/*physiology ; Mutation ; Mutation, Missense ; Phosphorylation/physiology

Sptrx-1, 2 and 3 are a series of thioredoxins specifically expressed in the testis/sperm. They play a significant role structurally and functionally in the process of spermiogenesis. The genesis and mutation of sptrx-1, 2 and 3 are correlated to male reproduction. Taking sptrx-1, 2 and 3 as the target of study and treatment will open up a new field in the clinical study of male reproduction.
Humans ; Male ; Mutation ; Spermatogenesis ; genetics ; physiology ; Spermatozoa ; chemistry ; cytology ; metabolism ; Testis ; chemistry ; cytology ; metabolism ; Thioredoxins ; biosynthesis ; genetics ; physiology

INTRODUCTIONCommon obesity is a multi-factorial trait, contributed by the "obesogenic" environment of caloric abundance and increasing automation, sedentary lifestyle and an underlying genetic susceptibility. There have been major advances in the past decade in our understanding of the human weight regulation mechanism and pathogenesis of obesity, abetted by discoveries of genetic defects which lead to human obesity.

MATERIALS AND METHODSReports of genetic mutations causing obesity in humans and murine models were reviewed.

RESULTSHumans with genetic defects resulting in leptin deficiency, leptin receptor deficiency, proopiomelanocortin deficiency (POMC), and melanocortin 4 receptor (MC4R) deficiency developed severe obesity as the dominant phenotypic feature, though these are rare autosomal recessive conditions, except MC4R deficiency which is inherited in an autosomal co-dominant fashion. Common and rare variants of the POMC and melanocortin 3 receptor genes may be predisposing factors in the development of common obesity. Recent reports of human obesity associated with thyrosine kinase B (TrkB) defect and brain derived neurotrophic factor (BDNF) disruption, coupled with other murine studies, supported the role of BDNF/TrkB as effectors downstream of the melanocortin receptors.

CONCLUSIONDespite exciting discoveries of single gene mutations resulting in human obesity, most cases of obesity are likely the result of subtle interactions of several related genetic variants with environmental factors which favour the net deposition of calories as fat, culminating in the obese phenotype. The mechanisms of action of these genes in the development of obesity are now being examined, with the aim of eventually discovering a therapeutic intervention for obesity.

Animals ; Body Weight ; genetics ; Disease Models, Animal ; Humans ; Leptin ; genetics ; physiology ; Melanocortins ; genetics ; physiology ; Mice ; Mutation ; Obesity ; genetics

OBJECTIVETo summarize the results of general survey, primary structure analysis and related functional studies of abnormal hemoglobins (Hbs) found in Hunan Province.

DATA SOURCESInternational Hb journals, Chinese biochemical and biomedical journals and other articles relevant to hematology.

STUDY SELECTIONAll Hb variants found in Hunan and identified by primary structure analysis during 1980 - 1991 were included.

DATA EXTRACTIONData concerning 11 types of Hb variants found in 3 districts and 7 counties in Hunan Province were briefly documented. Their frequencies of occurrence were calculated and their distributions among Han, Yao, Tujia and Dong ethnic groups were listed.

RESULTSThirty-six cases with abnormal Hb were identified out of 7412 individuals screened in Hunan. 11 different types of Hb variants were recognized by primary structure analysis in 19 propositi along with their family members, including 5 alpha-chain variants, 4 beta-chain variants, 1 delta-chain variant and 1 delta-beta chain fusion variant. Oxygen equilibrium characteristics, reaction dynamics, the rate of globin chain synthesis (RGCS), morphology observation by electron microscopy and DNA analysis were all used in the functional studies of hemoglobinopathies.

CONCLUSIONSThe average incidence of abnormal Hbs in Hunan is 0.486%. In Jianghua County, whose inhabitants are mostly of the Yao ethnic group, the incidence is significantly higher (1.09%). Hb Jianghua [beta120(GH3) Lys-->lle] and Hb Shuangfeng (SF) [alpha27(B8) Glu-->Lys] were two new variants first reported in international literature; whereas Hb Lille [alpha74(EF3) Asp-->Ala], HbA(2) Flatbush [delta22(B4) Ala-->Glu] and Hb Lepore-Boston [delta87(F3)-beta116(G18)] were the first three instances to be found in China. Hb SF displayed an oxygen affinity 1.5-fold higher than that of HbA at pH 7.4 and 25 degrees C with its oxygen equilibrium curve shifted to the left. Reticulocytes of Hb SF heterozygote showed unbalanced RGCS, quite similar to that found in beta-thalassemia minor. Erythrocytes of Hb SF heterozygote were changed to spherocytes and began to lyse after incubation with sodium salicylate or sulfadiazine (pH 7.4, 37 degrees C) for 2 - 4 h. These findings explained the sudden attack of hemolytic anemia provoked by two drugs in Hb SF propositus. The genotype of a patient with Hb Q-H disease is identified as -,-/-,alpha(Q) by DNA restriction mapping.

Erythrocytes ; drug effects ; Globins ; biosynthesis ; Hemoglobins, Abnormal ; chemistry ; genetics ; physiology ; Humans ; Mutation