Cell cycle control and plant morphogenesis: is there an essential link?

Plant morphogenesis has some interesting features that may have consequences for the regulation of cell division. In particular, the immobility of plant cells implies the necessity for highly accurate controls, in contrast with the flexibility of many developmental processes in animals. An important question in plant development concerns the status of the relationship between plant morphogenesis and cell division. In this review, we discuss the current knowledge of the molecular mechanisms controlling the plant cell cycle and how this could be differentially regulated during plant morphogenesis. The plant genes involved are homologous to those of other higher eukaryotes, suggesting a similar cell cycle machinery. A variety of mechanisms control these genes, reflecting the complexity of internal and environmental signals to which plants should respond. This intricate network requires an upstream control mechanism to function as a failsafe system and to govern cell division and growth to produce the correct plant shape. BioEssays 21:29–37, 1999. © 1999 John Wiley & Sons, Inc.     

Why is entry exclusion an essential feature of conjugative plasmids?

Entry exclusion is a property of plasmids by which the cells that contain them become bad recipients in additional conjugation rounds. This work reviews entry exclusion essential features and analyzes the mechanisms of action of the best studied systems. We searched for homologs of the proteins responsible for experimentally known exclusion systems. Results were used to classify exclusion systems in families of related elements. We arrive to the conclusion that all conjugative plasmids contain at least one entry exclusion gene. Although entry exclusion genes seem to be part of the plasmid conjugative machinery, they are systematically absent in phylogenetically related type IV protein exporting machines involved in virulence for plants and animals. We infer from this fact that entry exclusion is an essential feature of conjugative plasmid biology. Mathematical models suggest that plasmids expressing entry exclusion selectively eliminate plasmids lacking it, reinforcing its essential character and suggesting that entry exclusion plays a direct role in plasmid survival. Other experimental results confirm that entry exclusion is essential for the stability of a conjugative plasmid. We suggest that entry exclusion limits the damage of lethal zygosis (bacterial death produced by excessive rounds of conjugation). Additionally, it avoids competition in a host among identical plasmid backbones. Conversely, the lack of entry exclusion in conjugative transposons can be understood as a means of generating rapid evolutionary change.     

HP1 proteins—What is the essential interaction?

There are three mammalian HP1 genes, Cbx5 (encoding HP1α), Cbx1 (encoding HP1β) and Cbx3 (encoding (HP1γ). Despite their high degree of sequence homology mutational analysis has revealed different phenotypes indicating that they possess different functions. Notably, the Cbx1 mutation is lethal in its homozygous condition. The Cbx1 null phenotype is therefore more severe than the Suv(3)9h1/h2 double-mutant mouse, indicating that the essential function of the Cbx1 gene product, HP1β, is likely to lie outside its interaction with the heterochromatic H3K9me3 determinant of the “histone code” imposed by the Suv(3)9h1/h2 HMTases. Comparisons of HP1 mutants in flies and fungi with corresponding mutations in Suv(3)9 genes show that HP1 mutations are invariably more severe than mutation in Suv(3)9 genes. The implications of these data for HP1 function are discussed.     

α1β1-Integrin is an essential signal for neurite outgrowth induced by thrombospondin type 1 repeats of SCO-spondin

In the central and peripheral nervous systems a heterogeneous group of proteins constituting the thrombospondin superfamily provides a cue for axonal pathfinding. They either contain or are devoid of the tripeptide RGD, and the sequence(s) and mechanism(s) which trigger in vitro their neurite-promoting activity have remained unclear. In this study, we reconsider the problem of whether sequences present in the thrombospondin type 1 repeats (TSRs), and independent of the well-known RGD-binding site, may activate integrins and account for their neurite-promoting activity. SCO-spondin is a newly identified member of the thrombospondin superfamily, which shows a multidomain organization with a great number of TSR motifs but no RGD sequence. Previous research has implicated oligopeptides derived from SCO-spondin TSRs in in-vitro development of various neuronal cell types. In this study, we investigate whether function-blocking antibodies directed against integrin subunits can block these effects in cell line B104, cloned from a neuroblastoma of the rat central nervous system. By two different approaches: flow cytometry revealing short-term effects and cell cultures revealing long-term effects, we show that: (a) activation of cell metabolism, (b) changes in cell size and structure, and (c) neurite-promoting activity induced by TSR oligopeptides are inhibited by function-blocking antibodies to 1-subunit. Using a panel of function-blocking antibodies directed against various integrin -subunits we show that the 1-subunit might be the partner of the 1-subunit in B104 cells. Thus, we demonstrate that an original sequence within a TSR motif from SCO-spondin promotes neurite outgrowth through an intracellular signal driven by integrins, independently of an RGD-binding site.     

Programmed cell death in trypanosomatids: is it an altruistic mechanism for survival of the fittest?

The protozoan parasites Leishmania, Trypanosoma cruzi and Trypanosoma brucei show multiple features consistent with a form of programmed cell death (PCD). Despite some similarities with apoptosis of mammalian cells, PCD in trypanosomatid protozoans appears to be significantly different. In these unicellular organisms, PCD could represent an altruistic mechanism for the selection of cells, from the parasite population, that are fit to be transmitted to the next host. Alternatively, PCD could help in controlling the population of parasites in the host, thereby increasing host survival and favoring parasite transmission, as proposed by Seed and Wenk. Therefore, PCD in trypanosomatid parasites may represent a pathway involved both in survival and propagation of the species.     

Antigenic polymorphism in malaria: is it an important mechanism for immune evasion?

Malarial infections do not readily evoke an effective protective immunity against re-infection. Possible reasons for this include the ability of the parasites to interfere with the host's immune response and to evade the response in an immune host, by, for example, exploiting antigenic polymorphism or variation. Antigenic polymorphism undoubtedly exists in malaria parasite populations but does this polymorphism actually contribute to immune evasion by the parasite? Here, Kamini Mendis and colleagues examine the evidence for this and its implications for future malaria vaccines.     

Is kinase activity essential for biological functions of BRI1?

Brassinosteroids (BRs) are a major group of plant hormones that regulate plant growth and development. BRI1, a protein localized to the plasma membrane, functions as a BR receptor and it has been proposed that its kinase activity has an essential role in BR-regulated plant growth and development. Here we report the isolation and molecular characterization of a new allele of bri1, bri1-301, which shows moderate morphological phenotypes and a reduced response to BRs under normal growth conditions. Sequence analysis identified a two-base alteration from GG to AT, resulting in a conversion of 989G to 989I in the BRI1 kinase domain. An in vitro assay of kinase activity showed that bri1-301 has no detectable autophosphorylation activity or phosphorylation activity towards the BRI1 substrates TTL and BAK1. Furthermore, our results suggest that bri1-301, even with extremely impaired kinase activity, still retains partial function in regulating plant growth and development, which raises the question of whether BRI1 kinase activity is essential for BR-mediated growth and development in higher plants.     

Vasodilatory effects of cholecystokinin: new role for an old peptide?

Cholecystokinin (CCK) peptides are involved in the control of multiple functions both in the central nervous system (CNS) and in the gastrointestinal tract where they act as neurotransmitters and regulate digestive functions. This review deals with the role of CCK peptides as vasoactive mediators. Recent work from our group demonstrates that CCK peptides induce neurogenic vasodilatation both in cerebral and mesenteric vessels. Such an effect is mediated by nitric oxide and seems to be presynaptic. These findings suggest that endogenous CCK peptides could be relevant vasodilatory agents involved in regulating both cerebral and splanchnic blood flow. We hypothesize here how such an effect could be useful in the interpretation of, in a new conceptual frame, the eventual contribution of CCK to some physiological and physiopathological events, such as splanchnic postprandial hyperaemia, panic attack or migraine.     

What is the role of autophagy in HIV-1 infection?

HIV-1 infection is characterized by a progressive CD4 T cell depletion. It is now accepted that apoptosis of uninfected bystander CD4 T lymphocytes plays a major role in AIDS development. Viral envelope glycoproteins (Env) are mainly involved in inducing this cell death process, but the mechanisms triggered by HIV-1 leading to immunodeficiency are still poorly understood. Recently, we have demonstrated that autophagy is a prerequisite for Env-mediated apoptosis in uninfected CD4 T cells, underlining its role in HIV-1 infection. However, occurrence of autophagy in HIV-1-infected cells has not yet been described. Several hypotheses are discussed, based on the comparison with data from other viral infections.     

What is the role of autophagy in HIV-1 infection?

HIV-1 infection is characterized by a progressive CD4 T cell depletion. It is now accepted that apoptosis of uninfected bystander CD4 T lymphocytes plays a major role in AIDS development. Viral envelope glycoproteins (Env) are mainly involved in inducing this cell death process, but the mechanisms triggered by HIV-1 leading to immunodeficiency are still poorly understood. Recently, we have demonstrated that autophagy is a prerequisite for Env-mediated apoptosis in uninfected CD4 T cells, underlining its role in HIV-1 infection. However, occurrence of autophagy in HIV-1-infected cells has not yet been described. Several hypotheses are discussed, based on the comparison with data from other viral infections.     

Autophagy: an overlooked mechanism of HIV-1 pathogenesis and neuroAIDS?

Human immunodeficiency virus type 1 (HIV-1) establishes a persistent infection characterized by progressive depletion of CD4(+) lymphocytes and immunosuppression. Although extensive research has examined the importance of apoptosis as a cause of cell death associated with HIV-1 infection, the role of autophagy has been largely ignored. Our laboratory has examined the autophagic process in HIV-1-infected cells. Following infection of human peripheral blood CD4(+) T-cells or U937 cells with HIV-1 for 48 hours, the autophagy proteins Beclin 1 and LC3-II were found to be markedly decreased. Beclin 1 mRNA expression and autophagosomes were also reduced in HIV-1 infected cells. Thus, our data indicate that HIV-1 infection inhibits autophagy in infected cells in contrast to the previously described induction of autophagy by gp120 in uninfected bystander cells. It is likely that HIV-1 has evolved this mechanism as part of an elaborate attempt to evade the immune system while promoting its own replication. We believe that autophagy is an overlooked mechanism in HIV-1 pathogenesis and plays a particularly important role in the early cognitive impairment and dementia often associated with advanced AIDS. A model is presented that describes the potential role of autophagy in NeuroAIDS.