Progress in glial cell studies in some laboratories in China

Glial cells in the central nervous system(CNS) consist of a heterogeneous population of cell types,each characterized by distinct morphological features,physiological properties,and specific markers.In contrast to the previous view that glial cells were passive elements in the brain,accumulating evidence suggests that glial cells are active participants in various brain functions and brain disorders.This review summarizes recent progress of glial cell studies from several groups in China,ranging from studie...     

The cellular and subcellular localization of neuroglobin and cytoglobin -- a clue to their function?

Neuroglobin and cytoglobin are recently discovered respiratory proteins of vertebrates with yet ill-defined physiological functions. Neuroglobin is widely expressed in neurons, but not glia, in the vertebrate central and peripheral nervous systems. Other major expression sites are the retina and endocrine tissues. This distribution is indicative of a function of neuroglobin in metabolically most active, oxygen-consuming cell types, but does not yet allow to safely distinguish between different cellular roles, such as oxygen homeostasis, scavenging of reactive oxygen species or sustaining energy metabolism. Cytoglobin is predominantly expressed in connective tissue fibroblasts and related cell types in the body organs. Its main function may therefore be related to the specific amounts of extracellular matrix. Cytoglobin may hypothetically be involved in the oxygen-consuming maturation of collagen proteins. Cytoglobin is also expressed in distinct cell types of brain and retina. Its distribution strikingly differs from neuroglobin, suggesting an independent, yet unknown function.     

Functions of prion protein PrPc

It is now well established that both normal and pathological (or scrapie) isoforms of prion protein, PrPc and PrPsc respectively, are involved in the development and progression of various forms of neurodegenerative diseases, including scrapie in sheep, bovine spongiform encephalopathy (or "mad cow disease") and Creutzfeldt-Jakob disease in human, collectively known as prion diseases. The protein PrPc is highly expressed in the central nervous system in neurons and glial cells, and also present in non-brain cells, such as immune cells or epithelial and endothelial cells. Identification of the physiological functions of PrPc in these different cell types thus appears crucial for understanding the progression of prion diseases. Recent studies highlighted several major roles for PrPc that may be considered in two major domains : (1) cell survival (protection against oxidative stress and apoptosis) and (2) cell adhesion. In association with cell adhesion, distinct functions of PrPc were observed, depending on cell types : neuronal differentiation, epithelial and endothelial barrier integrity, transendothelial migration of monocytes, T cell activation. These observations suggest that PrPc functions may be particularly relevant to cellular stress, as well as inflammatory or infectious situations.     

Purinoceptors on Neuroglia

Purinergic transmission is one of the most ancient and widespread extracellular signalling systems. In the brain, purinergic signalling plays a unique role in integrating neuronal and glial cellular circuits, as virtually every type of glial cell possesses receptors to purines and pyrimidines. These receptors, represented by metabotropic P1 adenosine receptors, metabotropic P2Y purinoceptors and ionotropic P2X purinoceptors, control numerous physiological functions of glial cells and are intimately involved in virtually every form of neuropathology. In this essay, we provide an in depth overview of purinoceptor distribution in two types of CNS glia—in astrocytes and oligodendrocytes—and discuss their physiological and pathophysiological roles. An erratum to this article can be found at     

Differential inositol 1,4,5-trisphosphate receptor signaling in a neuronal cell line

Differential intracellular distribution of the three pharmacologically and biophysically distinct types of IP3Rs can lead to different subcellular Ca2+ transients each coupled to discrete intracellular functions. Here, we report the functional localization of differentially distributed IP3 receptor types in the commonly-used hippocampal cell line HT22. The distinct subcellular localization and Ca2+ signaling properties of these receptors determine the potential role of specific IP3 receptor types in cellular function. By utilizing immunochemistry, we conclude that HT22 cells express all three IP3 receptors with types 1 and 3 being expressed predominantly in the endoplasmic reticulum and perinuclear regions and type 2 being expressed predominantly in the nuclear envelope. Optical imaging studies using the Ca2+-sensitive indicator dye fluo-3 show that nuclear IP3 responses have greater amplitude and faster kinetics than cytosolic IP3 responses corresponding to the biophysical characteristics of the differentially distributed receptor types. These results support the hypothesis that differentially distributed IP3R isotypes mediate distinct cellular functions through differential, organelle-specific Ca2+ signaling.     

Complexity of the TOR signaling network

The target of rapamycin (TOR) is a serine/threonine kinase of the phosphatidylinositol kinase-related kinase family and is highly conserved from yeast to mammals. TOR functions as a central regulator of cell growth and is itself regulated by a wide range of signals, including growth factors, nutrients and stress conditions. Recent studies in eukaryotic cells have identified two distinct TOR complexes, TORC1 and TORC2, which phosphorylate different substrates and have distinct physiological functions. Here, we discuss new findings that have extended the complexity of TOR signaling and the different roles of the TORC complexes in yeast, flies and mammals.     

Insight into Actin Organization and Function in Cytokinesis from Analysis of Fission Yeast Mutants

Actin is a key cytoskeletal protein with multiple roles in cellular processes such as polarized growth, cytokinesis, endocytosis, and cell migration. Actin is present in all eukaryotes as highly dynamic filamentous structures, such as linear cables and branched filaments. Detailed investigation of the molecular role of actin in various processes has been hampered due to the multifunctionality of the protein and the lack of alleles defective in specific processes. The actin cytoskeleton of the fission yeast, Schizosaccharomyces pombe, has been extensively characterized and contains structures analogous to those in other cell types. In this study, primarily with the view to uncover actin function in cytokinesis, we generated a large bank of fission yeast actin mutants that affect the organization of distinct actin structures and/or discrete physiological functions of actin. Our screen identified 17 mutants with specific defects in cytokinesis. Some of these cytokinesis mutants helped in dissecting the function of specific actin structures during ring assembly. Further genetic analysis of some of these actin mutants revealed multiple genetic interactions with mutants previously known to affect the actomyosin ring assembly. We also characterize a mutant allele of actin that is suppressed upon overexpression of Cdc8p-tropomyosin, underscoring the utility of this mutant bank. Another 22 mutant alleles, defective in polarized growth and/or other functions of actin obtained from this screen, are also described in this article. This mutant bank should be a valuable resource to study the physiological and biochemical functions of actin.     

The cytology,histochemistry, and ultrastructure of the cell types found in the digestive gland of the slug,Agriolimax reticulatus (Müller)

Summary Four cell types have been identified in the digestive glands from light and electron microscope studies. The possible functions of each cell type are discussed.Thin cells are undifferentiated. Calcium cells contain spherules of calcium salts which have a characteristic ultrastructure. Different protein granules are found apically. Digestive cells are present as two distinct forms. One form is believed to be absorbing food material and digesting it intracellularly, and the other form is a secreting cell. Both forms contain green and yellow granules and histochemistry shows these granules to be distinct. Protein granules also occur apically.Excretory cells are distinguished by having a large central vacuole containing excretory granules. Histochemistry shows these granules, like the yellow granules of digestive cells, to be composed mainly of lipofuscin.It is suggested that digestive cells form excretory cells.     

Origin of new glial cells in intact and injured adult spinal cord

Several distinct cell types in the adult central nervous system have been suggested to act as stem or progenitor cells generating new cells under physiological or pathological conditions. We have assessed the origin of new cells in the adult mouse spinal cord by genetic fate mapping. Oligodendrocyte progenitors self-renew, give rise to new mature oligodendrocytes, and constitute the dominating proliferating cell population in the intact adult spinal cord. In contrast, astrocytes and ependymal cells, which are restricted to limited self-duplication in the intact spinal cord, generate the largest number of cells after spinal cord injury. Only ependymal cells generate progeny of multiple fates, and neural stem cell activity in the intact and injured adult spinal cord is confined to this cell population. We provide an integrated view of how several distinct cell types contribute in complementary ways to cell maintenance and the reaction to injury.     

Downstream of homeotic genes: in the heart of Hox function

A functional organ is constituted of diverse cell types. Each one occupies a distinct position and is associated to specific morphological and physiological functions. The identification of the genetic programs controlling these elaborated and highly precise features of organogenesis is crucial to understand how a mature organ works under normal conditions, and how pathologies can develop. Recently, a number of studies have reported a critical role for Hox genes in one example of organogenesis: cardiogenesis in Drosophila. Beyond the interest in understanding the molecular basis of functional cardiogenesis, this system might provide a model for proposing new paradigms of how Hox genes achieve their action throughout development.     

Why stem/progenitor cells lose their regenerative potential

Nowadays, it is clear that adult stem cells, also called as tissue stem cells, play a central role to repair and maintain the tissue in which they reside by their self-renewal ability and capacity of differentiating into distinct and specialized cells. As stem cells age, their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired. From a molecular perspective, these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration (i.e epigenomic profile) as well as changes in the tissue microenviroment, both into the niche and by systemic circulating factors. Strikingly, it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Therefore, understanding how resident stem cell age and affects near and distant tissues is fundamental. Here, we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number, function and phenotype that determine the loss of tissue renewal properties. Furthermore, we examine the possible cell rejuvenation strategies. Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.     

A simple,chisel-assisted mechanical microdissection system for harvesting homogenous plant tissue suitable for the analysis of nucleic acids and proteins

Many physiological processes are limited to specific tissues or even specific cell types. Analysing entire plants or organs results in averaged data of all cell types contained in the sample; thus, specific metabolic functions cannot be assigned to individual cell types. A higher spatial resolution is required. By microdissecting plant organs, homogeneous material can be obtained. If a suitable amount of material is collected, standard analytical methods can be applied to elucidate cell type-specific processes. The collection of sufficient quantities of homogeneous material can be done by means of mechanical microdissection. This technique is a low-cost alternative to laser-coupled microdissection techniques. Here we describe a protocol for chisel-assisted mechanical microdissection of embedded plant material and demonstrate that the collected material is suitable to obtain nucleic acids and proteins.     

Kinomics: methods for deciphering the kinome

Phosphorylation by protein kinases is the most widespread and well-studied signaling mechanism in eukaryotic cells. Phosphorylation can regulate almost every property of a protein and is involved in all fundamental cellular processes. Cataloging and understanding protein phosphorylation is no easy task: many kinases may be expressed in a cell, and one-third of all intracellular proteins may be phosphorylated, representing as many as 20,000 distinct phosphoprotein states. Defining the kinase complement of the human genome, the kinome, has provided an excellent starting point for understanding the scale of the problem. The kinome consists of 518 kinases, and every active protein kinase phosphorylates a distinct set of substrates in a regulated manner. Deciphering the complex network of phosphorylation-based signaling is necessary for a thorough and therapeutically applicable understanding of the functioning of a cell in physiological and pathological states. We review contemporary techniques for identifying physiological substrates of the protein kinases and studying phosphorylation in living cells.     

远端上游元件结合蛋白1的生物学功能

远端上游元件结合蛋白1（far upstream element binding protein 1, FUBP1）通过特异性结合远端上游元件（upstream element, FUSE）调控原癌基因c-Myc的转录。FUBP家族包括FUBP1、FUBP2、FUBP3及FUBP4,其序列具有高度同源性,但功能各不相同。FUBP1蛋白由3个结构域构成,具有两亲性螺旋结构的N端、富含酪氨酸的C端以及1个DNA结合区域。生理状态下,FUBP1蛋白定位于细胞核。除了调控c-Myc转录外,FUBP1还可结合RNA,参与调控mRNA稳定性、病毒复制及RNA的剪接。     

Podosome-type adhesions and focal adhesions, so alike yet so different

Cell-matrix adhesions are essential for cell migration, tissue organization and differentiation, therefore playing central roles in embryonic development, remodeling and homeostasis of tissues and organs. Matrix adhesion-dependent signals cooperate with other pathways to regulate biological functions such as cell survival, cell proliferation, wound healing, and tumorigenesis. Cell migration and invasion are integrated processes requiring the continuous, coordinated assembly and disassembly of integrin-mediated adhesions. An understanding of how integrins regulate cell migration and invasiveness through the dynamic regulation of adhesions is fundamental to both physiological and pathological situations. A variety of cell-matrix adhesions has been identified, namely, focal complexes, focal adhesions, fibrillar adhesions, podosomes, and invadopodia (podosome-type adhesions). These adhesion sites contain integrin clusters able to develop specialized structures, which are different in their architecture and dynamics although they share almost the same proteins. Here we compare recent advances and developments in the elucidation of the organization and dynamics of focal adhesions and podosome-type adhesions, in order to understand how such subcellular sites - though closely related in their composition - can be structurally and functionally different. The underlying question is how their respective physiological or pathological roles are related to their distinct organization.     

Senescent cells and macrophages: key players for regeneration?

Over the last decade, our understanding of the physiological role of senescent cells has drastically evolved, from merely indicators of cellular stress and ageing to having a central role in regeneration and repair. Increasingly, studies have identified senescent cells and the senescence-associated secretory phenotype (SASP) as being critical in the regenerative process following injury; however, the timing and context at which the senescence programme is activated can lead to distinct outcomes. For example, a transient induction of senescent cells followed by rapid clearance at the early stages following injury promotes repair, while the long-term accumulation of senescent cells impairs tissue function and can lead to organ failure. A key role of the SASP is the recruitment of immune cells to the site of injury and the subsequent elimination of senescent cells. Among these cell types are macrophages, which have well-documented regulatory roles in all stages of regeneration and repair. However, while the role of senescent cells and macrophages in this process is starting to be explored, the specific interactions between these cell types and how these are important in the different stages of injury/reparative response still require further investigation. In this review, we consider the current literature regarding the interaction of these cell types, how their cooperation is important for regeneration and repair, and what questions remain to be answered to advance the field.     

Chloride channels: An emerging molecular picture

Chloride channels are probably found in every cell, from bacteria to mammals. Their physiological tasks range from cell volume regulation to stabilization of the membrane potential, signal transduction, transepithelial transport and acidification of intracellular organelles. These different functions require the presence of many distinct chloride channels, which are differentially expressed and regulated by various stimuli. These include various intracellular messengers (like calcium and cyclic AMP), pH, extracellular ligands and transmembrane voltage. Three major structural classes of chloride channels are known to date, but there may be others not yet identified. After an overview of the general functions of chloride channels, this review will focus on these cloned chloride channels: the CLC chloride channel family, which includes voltage-gated chloride channels, and the cystic fibrosis transmembrane regulator (CFTR), which performs other functions in addition to being a chloride channel. Finally, a short section deals with GABA and glycine receptors. Diseases resulting from chloride channel defects will be specially emphasized, together with the somewhat limited information about how these proteins work at the molecular level.     

Caspases: evolutionary aspects of their functions in vertebrates

Caspases (cysteine-dependent aspartyl-specific protease) belong to a family of cysteine proteases that mediate proteolytic events indispensable for biological phenomena such as cell death and inflammation. The first caspase was identified as an executioner of apoptotic cell death in the worm Caenorhabditis elegans . Additionally, a large number of caspases have been identified in various animals from sponges to vertebrates. Caspases are thought to play a pivotal role in apoptosis as an evolutionarily conserved function; however, the number of caspases that can be identified is distinct for each species. This indicates that species-specific functions or diversification of physiological roles has been cultivated through caspase evolution. Furthermore, recent studies suggest that caspases are also involved in inflammation and cellular differentiation in mammals. This review highlights vertebrate caspases in their universal and divergent functions and provides insight into the physiological roles of these molecules in animals.