Pigments,Parasites and Personalitiy: Towards a Unifying Role for Steroid Hormones?

A surging interest in the evolution of consistent trait correlations has inspired research on pigment patterns as a correlate of behavioural syndromes, or "animal personalities". Associations between pigmentation, physiology and health status are less investigated as potentially conserved trait clusters. In the current study, lice counts performed on farmed Atlantic salmon Salmo salar naturally infected with ectoparasitic sea lice Lepeophtheirus salmonis showed that individual fish with high incidence of black melanin-based skin spots harboured fewer female sea lice carrying egg sacs, compared to less pigmented fish. There was no significant association between pigmentation and lice at other developmental stages, suggesting that host factors associated with melanin-based pigmentation may modify ectoparasite development to a larger degree than settlement. In a subsequent laboratory experiment a strong negative correlation between skin spots and post-stress cortisol levels was revealed, with less pigmented individuals showing a more pronounced cortisol response to acute stress. The observation that lice prevalence was strongly increased on a fraction of sexually mature male salmon which occurred among the farmed fish further supports a role for steroid hormones as mediators of reduced parasite resistance. The data presented here propose steroid hormones as a proximate cause for the association between melanin-based pigmentation and parasites. Possible fundamental and applied implications are discussed.     

ZW10 Function in Mitotic Checkpoint Control,Dynein Targeting,and Membrane Trafficking: Is Dynein the Unifying Theme?

ZW10 was initially identified as a mitotic checkpoint protein involved in chromosome segregation. It was subsequently implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, though the relationship between these functions remains incompletely understood. Recent studies have revealed that ZW10 performs important functions in non-dividing cells as well. These include cytoplasmic dynein targeting to Golgi and other membranes, but also SNARE-mediated ER-Golgi trafficking. Identifying a unifying function for ZW10 in these diverse contexts has been elusive, but likely involves cytoplasmic dynein, as discussed here.     

How a RING Finger Protein and a Steroid Hormone Control Autophagy?

Previous work in our laboratory has indicated that the steroid hormone ecdysone triggers programmed autophagy in the fat body of Drosophila larvae by downregulating the class I phosphoinositide 3-kinase (PI3K) pathway. We recently found evidence that Deep orange (Dor), a Drosophila RING finger protein implicated in late-endosomal trafficking, controls ecdysone signaling as well as autolysosome fusion, thus exerting a dual regulation of autophagy. We found that dor mutants are defective in programmed autophagy. The mutant larvae showed impaired upregulation of ecdysone signaling during development, accompanied by a failure to downregulate the PI3K pathway. Downregulation of the PI3K pathway could be restored by feeding the dor mutants with ecdysone. Even though ecdysone signaling and autophagy were impaired in the dor mutants, we detected an accumulation of autophagosomes in dor mutant fat bodies. This could probably be attributed to the failure of autophagosomes to fuse with lysosomes. In this Addendum we review these findings and provide some speculations about how Dor may control both ecdysone signalling and autolysosomal fusion.

Addendum to:

A Dual Function for Deep Orange in Programmed Autophagy in the Drosophila melanogaster Fat Body

K. Lindmo, A. Simonsen, A. Brech, K. Finley, T.E. Rusten and H. Stenmark

Exp Cell Res 2006; Epub ahead of print     

Neuronal Apoptosis: BH3-Only Proteins the Real Killers?

At present there is a poor understanding of the events that lead up to neuronal apoptosis that occurs in neurodegenerative diseases and following acute ischemic episodes. Apoptosis is critical for the elimination of unwanted neurons within the developing nervous system. The Bcl-2 family of proteins contains pro- and anti-apoptotic proteins that regulate the mitochondrial pathway of apoptosis. There is increasing interest in a subfamily of the Bcl-2 family, the BH3-only proteins, and their pro-apoptotic effects within neurons. Recently ischemic and seizure-induced neuronal injury has been shown to result in the activation of the BH3-only protein, Bid. This protein is cleaved and the truncated protein (tBid) translocates to the mitochondria. The translocation of tBid to the mitochondria is associated with the activation of outer mitochondrial membrane proteins Bax/Bak and the release of cytochrome C from the mitochondria. ER stress also has been implicated as a factor for the induction of apoptosis in ischemic neuronal injury. The induction of ER stress in hippocampal neurons has been shown to activate expression of bb3/PUMA, a member of the BH3-only gene family. Activation of PUMA is associated with the activation and clustering of the pro-apoptotic Bcl-2 family member Bax and the loss of cytochrome C from the mitochondria.     

Is There a Phylogenetic Signal in Prokaryote Proteins?

Using the sequence information from nine completely sequenced bacterial genomes, we extract 32 protein families that are thought to contain orthologous proteins from each genome. The alignments of these 32 families are used to construct a phylogeny with the neighbor-joining algorithm. This tree has several topological features that are different from the conventional phylogeny, yet it is highly reliable according to its bootstrap values. Upon closer study of the individual families used, it is clear that the strong phylogenetic signal comes from three families, at least two of which are good candidates for horizontal transfer. The tree from the remaining 29 families consists almost entirely of noise at the level of bacterial phylum divisions, indicating that, even with large amounts of data, it may not be possible to reconstruct the prokaryote phylogeny using standard sequence-based methods. Received: 22 November 1998 / Accepted: 17 February 1999     

How Fast Does a Signal Propagate through Proteins?

As the molecular basis of signal propagation in the cell, proteins are regulated by perturbations, such as mechanical forces or ligand binding. The question arises how fast such a signal propagates through the protein molecular scaffold. As a first step, we have investigated numerically the dynamics of force propagation through a single (Ala) protein following a sudden increase in the stretching forces applied to its end termini. The force propagates along the backbone into the center of the chain on the picosecond scale. Both conformational and tension dynamics are found in good agreement with a coarse-grained theory of force propagation through semiflexible polymers. The speed of force propagation of 50Å ps⁻¹ derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.     

Proteins That Fuse and Fragment Mitochondria in Apoptosis: Con-Fissing a Deadly Con-Fusion?

During apoptosis, mitochondria undergo multiple changes that culminate in the release of cytochrome c and other proapoptotic cofactors. Recently, a role for previously overlooked morphological changes, fission of the mitochondrial reticulum and remodeling of mitochondrial cristae, has been suggested in mammalian cells and in developmental apoptosis of C. elegans. Mitochondrial morphology is determined by fusion and fission processes, controlled by a growing set of “mitochondria-shaping” proteins, whose levels and function appear to regulate the mitochondrial pathways of cell death. Expression of pro-fusion proteins, as well as of inhibition of pro-fission molecules reduces apoptosis, suggesting a linear relationship between fragmentation and death. Mechanisms by which mitochondrial fragmentation promotes apoptosis and interactions between fragmentation and remodeling of the inner membrane are largely unclear. A tempting, unifying hypothesis suggests that fission is coupled to cristae remodeling to maximize cytochrome c release.     

Bacterial Endocytic Systems in Plants and Animals: Ca2+ as a Common Theme?

Intracellular interactions between bacteria and host cells are widespread in nature. In this review, the similarity between the infection processes of bacteria in plant and animal cells will be addressed. As paradigms, we selected the symbiosis between rhizobia and leguminous plants, and the survival of intracellular pathogenic bacteria in animal cells. The rhizobial symbiosis with leguminous plants is a model system for the study of plant-bacterium interactions. Through this interaction, the bacteria are released in a vacuole-like structure, called the symbiosome. The molecular processes, which lead to a functional symbiosome, are far from known. However, membrane fusion processes, and therefore also Ca²⁺, are crucial to establish this highly specialized organelle-like structure. A homologous system is the infection by certain bacterial pathogens of animal cells. These bacteria enter their host via phagocytosis and avoid the fusion with lysosomes, resulting in a membrane-bound vacuole in which the pathogens survive. The origin and maturation of this phagosome depends on Ca²⁺-signaling processes in the host cell and on proteins that regulate membrane fusion processes, such as SNAREs, Rab proteins, synaptotagmins and calmodulin. The aim of this review is to compare the endosymbiosis in leguminous plants with the surviving pathogens in animal host cells with a focus on Ca²⁺-signaling and membrane fusion-related processes. For both systems, the interaction starts with a bacterial entry of the host cell. It will be demonstrated that in both cases Ca²⁺ is a crucial second messenger. However, more emphasis will be put on the comparison of the later stages of infection, i.e., the formation of specialized bacteria-containing vacuoles. From structural, functional, and proteomic data, it is clear that phagosomes and symbiosomes are more related to each other than originally assumed. Proteins such as V-ATPases, calreticulin, phosphatidylinositol-3-kinase, Rab proteins, and SNAREs are present in both the phagosome and the symbiosome membrane, indicating that common cellular processes are used for building these intracellular organelles.     

Keep Your Fingers Off My DNA: Protein–Protein Interactions Mediated by C2H2 Zinc Finger Domains

Cys2-His2 (C2H2) zinc finger domains (ZFs) were originally identified as DNA-binding domains, and uncharacterized domains are typically assumed to function in DNA binding. However, a growing body of evidence suggests an important and widespread role for these domains in protein binding. There are even examples of zinc fingers that support both DNA and protein interactions, which can be found in well-known DNA-binding proteins such as Sp1, Zif268, and Ying Yang 1 (YY1). C2H2 protein–protein interactions (PPIs) are proving to be more abundant than previously appreciated, more plastic than their DNA-binding counterparts, and more variable and complex in their interactions surfaces. Here we review the current knowledge of over 100 C2H2 zinc finger-mediated PPIs, focusing on what is known about the binding surface, contributions of individual fingers to the interaction, and function. An accurate understanding of zinc finger biology will likely require greater insights into the potential protein interaction capabilities of C2H2 ZFs.