TRP channels: an overview

The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.     

T-box家族与心脏发育

T-box家族是目前新发现的一个转录因子家族,该家族成员均具有与Brachyury的T座位同源的DNA结合结构域,它们在许多物种的发育过程特别是心脏发育的过程中起着关键性的作用.目前,人们已经从系统发育学的角度对该家族的进化关系及表达进行了分析,对T-box基因功能的研究工作也正在开始,并且都取得了一些重要的成果.     

The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily.

The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily (TC #2.A.66) consists of four previously recognized families: (a) the ubiquitous multi-drug and toxin extrusion (MATE) family; (b) the prokaryotic polysaccharide transporter (PST) family; (c) the eukaryotic oligosaccharidyl-lipid flippase (OLF) family and (d) the bacterial mouse virulence factor family (MVF). Of these four families, only members of the MATE family have been shown to function mechanistically as secondary carriers, and no member of the MVF family has been shown to function as a transporter. Establishment of a common origin for the MATE, PST, OLF and MVF families suggests a common mechanism of action as secondary carriers catalyzing substrate/cation antiport. Most protein members of these four families exhibit 12 putative transmembrane alpha-helical segments (TMSs), and several have been shown to have arisen by an internal gene duplication event; topological variation is observed for some members of the superfamily. The PST family is more closely related to the MATE, OLF and MVF families than any of these latter three families are related to each other. This fact leads to the suggestion that primordial proteins most closely related to the PST family were the evolutionary precursors of all members of the MOP superfamily. Here, phylogenetic trees and average hydropathy, similarity and amphipathicity plots for members of the four families are derived and provide detailed evolutionary and structural information about these proteins. We show that each family exhibits unique characteristics. For example, the MATE and PST families are characterized by numerous paralogues within a single organism (58 paralogues of the MATE family are present in Arabidopsis thaliana), while the OLF family consists exclusively of orthologues, and the MVF family consists primarily of orthologues. Only in the PST family has extensive lateral transfer of the encoding genes occurred, and in this family as well as the MVF family, topological variation is a characteristic feature. The results serve to define a large superfamily of transporters that we predict function to export substrates using a monovalent cation antiport mechanism.     

Some KpnI family members are associated with the Alu family in the human genome

The structures of the termini and their flanking regions of two human KpnI family members were investigated. The two differed in length, but the starting sequence at one terminal (defined as the 5' terminal) was found to be common to both members. The Alu family sequence was found in the 5' flanking regions. The KpnI family sequence started several base-pairs downstream from the 3' end of the Alu family sequence. In both cases, the Alu family sequence was not flanked by the direct repeat sequence common to the Alu family. These two members showed no sequence homology in 3' terminal regions. Interestingly, the Alu family plus the KpnI family unit was found to be flanked by a direct repeat sequence of several base-pair length. Based on these findings, relationship between the Alu family and KpnI family is discussed.     

Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference

Microtubule (MT)-based motor proteins, kinesins and dyneins, play important roles in multiple cellular processes including cell division. In this study, we describe the generation and use of an Escherichia coli RNase III-prepared human kinesin/dynein esiRNA library to systematically analyze the functions of all human kinesin/dynein MT motor proteins. Our results indicate that at least 12 kinesins are involved in mitosis and cytokinesis. Eg5 (a member of the kinesin-5 family), Kif2A (a member of the kinesin-13 family), and KifC1 (a member of the kinesin-14 family) are crucial for spindle formation; KifC1, MCAK (a member of the kinesin-13 family), CENP-E (a member of the kinesin-7 family), Kif14 (a member of the kinesin-3 family), Kif18 (a member of the kinesin-8 family), and Kid (a member of the kinesin-10 family) are required for chromosome congression and alignment; Kif4A and Kif4B (members of the kinesin-4 family) have roles in anaphase spindle dynamics; and Kif4A, Kif4B, MKLP1, and MKLP2 (members of the kinesin-6 family) are essential for cytokinesis. Using immunofluorescence analysis, time-lapse microscopy, and rescue experiments, we investigate the roles of these 12 kinesins in detail.     

A study on family communication space (Part II)--A study on spatial utilization for, and familial consciousness of, family communication

Part II, based on the findings of Part I, tries to identify family Communication by delving into how it is actually practiced in view of spatial conditions within a house, and familial consciousness. Specific spatial conditions have been sampled of the housing of students at women's junior colleges, and how their family members mutually Communicate and evaluate it has been analyzed. Their views of "family" have also been examined. The findings are as follows: 1) The number of rooms, and the width of the room(s) used for family Communication are major determining factors in separating family Communication from other living activities. 2) The above separation is affected by whether family Communication is practiced in a Japanese-style room or a Western-style one. 3) The perceptual difference of the consent of "family" among a family members principally determines how they engage in family Communication and how they evaluate it. It has proved to be necessary to consider, for a spatial analysis, what kind of posture each member takes when mutually Communicating, seeking comfort and relaxation at home.     

Function and structure studies of GH family 31 and 97 α-glycosidases

A huge number of glycoside hydrolases are classified into the glycoside hydrolase family (GH family) based on their amino-acid sequence similarity. The glycoside hydrolases acting on α-glucosidic linkage are in GH family 4, 13, 15, 31, 63, 97, and 122. This review deals mainly with findings on GH family 31 and 97 enzymes. Research on two GH family 31 enzymes is described: clarification of the substrate recognition of Escherichia coli α-xylosidase, and glycosynthase derived from Schizosaccharomyces pombe α-glucosidase. GH family 97 is an aberrant GH family, containing inverting and retaining glycoside hydrolases. The inverting enzyme in GH family 97 displays significant similarity to retaining α-glycosidases, including GH family 97 retaining α-glycosidase, but the inverting enzyme has no catalytic nucleophile residue. It appears that a catalytic nucleophile has been eliminated during the molecular evolution in the same way as a man-made nucleophile mutant enzyme, which catalyzes the inverting reaction, as in glycosynthase and chemical rescue.     

The evolution of a family of short interspersed repeats in primate DNA

Summary Human DNA contains 300 nucleotide interspersed repeated sequences which mostly belong to a single family of sequences called the Alu family. This work examines the evolution of this family of sequences in primates. Bonnet monkey (Macaque radiata) DNA contains a predominant family of 300 nucleotide repeats which has nearly the same restriction map as the human Alu family and which hybridizes to human Alu family repeats under Southern blotting conditions. Prosimian (Galago crassicaudatus pangeniesis) DNA also contains a prominent group of 300 nucleotide long repeated sequences which does not have the same restriction sites as the human Alu family but which does hybridize to the human Alu family under reduced stringency conditions.     

GATA family members as inducers for cellular reprogramming to pluripotency

Members of the GATA protein family play important roles in lineage specification and transdifferentiation. Previous reports show that some members of the GATA protein family can also induce pluripotency in somatic cells by substituting for Oct4, a key pluripotency-associated factor. However, the mechanism linking lineage-specifying cues and the activation of pluripotency remains elusive. Here, we report that all GATA family members can substitute for Oct4 to induce pluripotency. We found that all members of the GATA family could inhibit the overrepresented ectodermal-lineage genes, which is consistent with previous reports indicating that a balance of different lineage-specifying forces is important for the restoration of pluripotency. A conserved zinc-finger DNA-binding domain in the C-terminus is critical for the GATA family to induce pluripotency. Using RNA-seq and ChIP-seq, we determined that the pluripotency-related gene Sall4 is a direct target of GATA family members during reprogramming and serves as a bridge linking the lineage-specifying GATA family to the pluripotency circuit. Thus, the GATA family is the first protein family of which all members can function as inducers of the reprogramming process and can substitute for Oct4. Our results suggest that the role of GATA family in reprogramming has been underestimated and that the GATA family may serve as an important mediator of cell fate conversion.     

Male participation in family planning: results from a qualitative study in Mpigi District, Uganda

The aim of this study was to determine men's perceptions about family planning and how they participate or wish to participate in family planning activities in Mpigi District, central Uganda. Four focus group discussions were conducted with married men and with family planning providers from both the government and private sector. In addition, seven key informants were interviewed using a semi-structured interview guide. The results indicate that men have limited knowledge about family planning, that family planning services do not adequately meet the needs of men, and that spousal communication about family planning issues is generally poor. However, almost all men approved of modern family planning and expressed great interest in participating. The positive change of the beliefs and attitudes of men towards family planning in the past years has not been recognized by family planning programme managers, since available services are not in line with current public attitudes. A more couple-oriented approach to family planning is needed. Measures could include, for example, recruiting males as family planning providers, offering more family planning counselling for couples, and promoting female-oriented methods with men and vice versa.     

A study of family communication space (Part I)--A preliminary study on how family communication is actually practiced

Housing science needs to concern itself with how to improve space for family communication because it plays an important role in human dwelling life. The purpose of this report (Parts I, II & III) is, hence, to elucidate various factors conditioning family communication, and spatial traits of the rooms where it is conducted, based on the survey of the households of students at women's junior colleges. Part I delves into what is specifically communicated within a family and how it is related with other living activities, by grasping how communication is practiced in everyday family life. A basic analysis is made as to how conscious a family members are of their mutual communication, and how rooms are used for it. It has become clear that family communication is closely related with meal-taking both behaviorally and spatially, and that different attitudes among a family members toward family communication cause different modes, and evaluations of it. It has proved to be necessary, for the further studies of family communication, to give an analytical perspective to an in-depth examination of how rooms in the target families are used and how every member views and evaluates their family communication.     

Retropositional parasitism of SINEs on LINEs: identification of SINEs and LINEs in elasmobranchs.

Some previously unidentified short interspersed repetitive elements (SINEs) and long interspersed repetitive element (LINEs) were isolated from various higher elasmobranchs (sharks, skates, and rays) and characterized. These SINEs, members of the HE1 SINE family, were tRNA-derived and were widespread in higher elasmobranches. The 3'-tail region of this SINE family was strongly conserved among elasmobranchs. The LINEs, members of the HER1 LINE family, encoded an amino acid sequence similar to that encoded by the chicken CR1 LINE family, and they contained a strongly conserved 3'-tail region in the 3' untranslated region. This tail region of the HER1 LINE family was almost identical to that of the HE1 SINE family. Thus, the HE1 SINE family and the HER1 LINE family provide a clear example of a pair of SINEs and LINEs that share the same tail region. Conservation of the secondary structures of the tail regions, as well as of the nucleotide sequences, between the HE1 SINE family and HER1 LINE family during evolution suggests that SINEs utilize the enzymatic machinery for retroposition of LINEs through the recognition of higher-order structures of the conserved 3'-tail region. A discussion is presented of the parasitism of SINEs on LINEs during the evolution of these retroposons.     

Function and Structure Studies of GH Family 31 and 97 α-Glycosidases

A huge number of glycoside hydrolases are classified into the glycoside hydrolase family (GH family) based on their amino-acid sequence similarity. The glycoside hydrolases acting on α-glucosidic linkage are in GH family 4, 13, 15, 31, 63, 97, and 122. This review deals mainly with findings on GH family 31 and 97 enzymes. Research on two GH family 31 enzymes is described: clarification of the substrate recognition of Escherichia coli α-xylosidase, and glycosynthase derived from Schizosaccharomyces pombe α-glucosidase. GH family 97 is an aberrant GH family, containing inverting and retaining glycoside hydrolases. The inverting enzyme in GH family 97 displays significant similarity to retaining α-glycosidases, including GH family 97 retaining α-glycosidase, but the inverting enzyme has no catalytic nucleophile residue. It appears that a catalytic nucleophile has been eliminated during the molecular evolution in the same way as a man-made nucleophile mutant enzyme, which catalyzes the inverting reaction, as in glycosynthase and chemical rescue.     

The 724 family of DNA sequences is interspersed about the pericentromeric regions of human acrocentric chromosomes

We describe the organization of the complex, interspersed 724 family of DNA sequences that is distributed in multiple copies about the pericentromeric region of human acrocentric chromosomes. 724 family members were isolated using an efficient recombination-based assay for nucleotide sequence homology to screen a human genomic library. Eight related but distinct 724 family members were isolated that hybridized to a total of 20 different human-genomic EcoRI DNA fragments spanning 100,000 base pairs. In contrast with tandemly clustered satellite and ribosomal DNA sequences also located on the short arms of human acrocentric chromosomes, 724 family members are interspersed. No evidence for local interspersion or homology between 724 family members and ribosomal or satellite DNA sequences was found. Juxtaposition of the complex 724 family to the nucleolus organizer region was a recent event in primate evolution. The unique organization of 724 family members on each of the five human acrocentric chromosomes indicates that the 724 family continues to evolve within the human karyotype.     

Evolutionary analysis of the mammalian M1 aminopeptidases reveals conserved exon structure and gene death

The members of the M1 aminopeptidase family share conserved domains, yet show functional divergence within the family as a whole. In order to better understand this family, this study analyzed the mammalian members in depth at exon, gene, and protein levels. The twelve human members, eleven rat members, and eleven mouse members were first analyzed in multiple alignments to visualize both reported and unreported conserved domains. Phylogenetic trees were then generated for humans, rats, mice, and all mammals to determine how closely related the homologs were and to gain insight to the divergence in the family members. This produced three groups with similarity within the family. Next, a synteny study was completed to determine the present locations of the genes and changes that had occurred. It became apparent that gene death likely resulted in the lack of one member in mouse and rat. Finally, an in-depth analysis of the exon structure revealed that nine members of the human family and eight in mouse, are highly conserved within the exon structure. Taken together, these results indicate that the M1 aminopeptidase family is a divergent family with three subgroups and that genetic evidence mirrors categorization of the family by enzymatic function.     

A computer simulation of evolutionary forces controlling the size of a multigene family

Summary A Monte Carlo-type simulation of the evolution of a multigene family was performed. The model was designed to study the selective forces which may control the size of a multigene family. As expected, we find that direct selection on the size of the multigene family can control its size. More important, we find that selection acting upon the family as a single functional unit, in conjunction with homologous but unequal crossing over, can also control the size of a multigene family.     

Hereditary nonpolyposis colorectal cancer family members' perceptions about the duty to inform and health professionals' role in disseminating genetic information

This study's aim was to ascertain hereditary nonpolyposis colorectal cancer (HNPCC) families' views on the duty to inform with particular focus on the role of health professionals in disseminating familial genetic information. Eighty members of 16 families with a clinical or molecular diagnosis of HNPCC completed qualitative interviews regarding views on family members' right to know and who should disseminate familial genetic information. Most indicated that everyone in the family should know about the presence of a mutation in the family, with family members themselves being the preferable informant, supported by health professionals who were seen as helpful in overcoming barriers. All but one respondent indicated that if a parent did not test and presumably did not inform his/her child about the family mutation, the child should be informed by other family members or by a health professional. Many were attuned to confidentiality concerns, but judged them to be outweighed by the importance of family members knowing about the mutation and undertaking proper surveillance. Respondents were more private about the disclosure of individual results to other family members, clearly distinguishing personal results from familial genetic information. These families with a hereditary colon cancer syndrome favor open sharing of genetic information within the family, and desire the supportive involvement of health care professionals in disseminating genetic information.