The namesake pit organ of pit vipers and other temperature-sensing snakes is a remarkable biological thermometer, one that converts infrared light into an electrical signal (Bullock and Diecke 1956). The organ is arranged like a pinhole camera, with a small outward-facing opening covering a pit membrane dense with neuronal projections. This geometry ensures that only light from a narrow angular cone lands on the membrane.
View Article and Find Full Text PDFIn eukaryotic cells, the budding and fusion of intracellular transport vesicles is carefully orchestrated in space and time. Locally, a vesicle's source compartment, its cargo, and its destination compartment are controlled by dynamic multi-protein specificity modules. Globally, vesicle constituents must be recycled to ensure homeostasis of compartment compositions.
View Article and Find Full Text PDFVesicle budding and fusion in eukaryotes depend on a suite of protein types, such as Arfs, Rabs, coats and SNAREs. Distinct paralogs of these proteins act at distinct intracellular locations, suggesting a link between gene duplication and the expansion of vesicle traffic pathways. Genome doubling, a common source of paralogous genes in fungi, provides an ideal setting in which to explore this link.
View Article and Find Full Text PDFEukaryotic cells use small membrane-enclosed vesicles to transport molecular cargo between intracellular compartments. Interactions between molecules on vesicles and compartments determine the source and target compartment of each vesicle type. The set of compartment and vesicle types in a cell define the nodes and edges of a transport graph known as the vesicle traffic network.
View Article and Find Full Text PDFThe Golgi apparatus, the main glycosylation station of the cell, consists of a stack of discontinuous cisternae. Glycosylation enzymes are usually concentrated in one or two specific cisternae along the cis-trans axis of the organelle. How such compartmentalized localization of enzymes is achieved and how it contributes to glycosylation are not clear.
View Article and Find Full Text PDFThe synthesis of eukaryotic glycans - branched sugar oligomers attached to cell-surface proteins and lipids - is organized like a factory assembly line. Specific enzymes within successive compartments of the Golgi apparatus determine where new monomer building blocks are linked to the growing oligomer. These enzymes act promiscuously and stochastically, causing microheterogeneity (molecule-to-molecule variability) in the final oligomer products.
View Article and Find Full Text PDFGlycosyltransferases are a large family of enzymes responsible for covalently linking sugar monosaccharides to a variety of organic substrates. These enzymes drive the synthesis of complex oligosaccharides known as glycans, which play key roles in inter-cellular interactions across all the kingdoms of life; they also catalyze sugar attachment during the synthesis of small-molecule metabolites such as plant flavonoids. A given glycosyltransferase enzyme is typically responsible for attaching a specific donor monosaccharide, via a specific glycosidic linkage, to a specific moiety on the acceptor substrate.
View Article and Find Full Text PDFTwo unicellular relatives of animals reveal that coordinated contractions of groups of cells using actomyosin predated animal multicellularity during evolution.
View Article and Find Full Text PDFThe genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell, these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remarkably high fidelity: experiments reveal that most virions contain precisely one copy of each of the eight RNA segments.
View Article and Find Full Text PDFThe invariant cell initiation mass measured in bacterial growth experiments has been interpreted as a minimal unit of cellular replication. Here we argue that the existence of such minimal units induces a coupling between the rates of stochastic cell division and death. To probe this coupling we tracked live and dead cells in populations treated with a ribosome-targeting antibiotic.
View Article and Find Full Text PDFUsing real-time TIRF microscopy imaging, we identify sites of clathrin and dynamin-independent CLIC/GEEC (CG) endocytic vesicle formation. This allows spatio-temporal localisation of known molecules affecting CG endocytosis; GBF1 (a GEF for ARF1), ARF1 and CDC42 which appear sequentially over 60 s, preceding scission. In an RNAi screen for BAR domain proteins affecting CG endocytosis, IRSp53 and PICK1, known interactors of CDC42 and ARF1, respectively, were selected.
View Article and Find Full Text PDFA eukaryotic cell contains multiple membrane-bound compartments. Transport vesicles move cargo between these compartments, just as trucks move cargo between warehouses. These processes are regulated by specific molecular interactions, as summarized in the Rothman-Schekman-Sudhof model of vesicle traffic.
View Article and Find Full Text PDFIntracellular membrane-bounded organelles of eukaryotic cells transiently contact the extracellular environment during endocytosis and secretion. Such contacts must be precisely timed to prevent leakage of cargo. I argue that early eukaryotes evolved organelle acidification as a way to detect and prevent leakage.
View Article and Find Full Text PDFWhat is the minimal set of cell-biological ingredients needed to generate a Golgi apparatus? The compositions of eukaryotic organelles arise through a process of molecular exchange via vesicle traffic. Here we statistically sample tens of thousands of homeostatic vesicle traffic networks generated by realistic molecular rules governing vesicle budding and fusion. Remarkably, the plurality of these networks contain chains of compartments that undergo creation, compositional maturation, and dissipation, coupled by molecular recycling along retrograde vesicles.
View Article and Find Full Text PDFIf eukaryotes arose through a merger between archaea and bacteria, what did the first true eukaryotic cell look like? A major step toward an answer came with the discovery of Lokiarchaeum, an archaeon whose genome encodes small GTPases related to those used by eukaryotes to regulate membrane traffic. Although 'Loki' cells have yet to be seen, their existence has prompted the suggestion that the archaeal ancestor of eukaryotes engulfed the future mitochondrion by phagocytosis. We propose instead that the archaeal ancestor was a relatively simple cell, and that eukaryotic cellular organization arose as the result of a gradual transfer of bacterial genes and membranes driven by an ever-closer symbiotic partnership between a bacterium and an archaeon.
View Article and Find Full Text PDFMol Biochem Parasitol
November 2017
Microbial eukaryotes present a stunning diversity of endomembrane organization. From specialized secretory organelles such as the rhoptries and micronemes of apicomplexans, to peroxisome-derived metabolic compartments such as the glycosomes of kinetoplastids, different microbial taxa have explored different solutions to the compartmentalization and processing of cargo. The basic secretory and endocytic system, comprising the ER, Golgi, endosomes, and plasma membrane, as well as diverse taxon-specific specialized endomembrane organelles, are coupled by a complex network of cargo transport via vesicle traffic.
View Article and Find Full Text PDFMessenger RNA (mRNA) dynamics in single cells are often modeled as a memoryless birth-death process with a constant probability per unit time that an mRNA molecule is synthesized or degraded. This predicts a Poisson steady-state distribution of mRNA number, in close agreement with experiments. This is surprising, since mRNA decay is known to be a complex process.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2015
Eukaryotic cells use dynamins-mechano-chemical GTPases--to drive the division of endosymbiotic organelles. Here we probe early steps of mitochondrial and chloroplast endosymbiosis by tracing the evolution of dynamins. We develop a parsimony-based phylogenetic method for protein sequence reconstruction, with deep time resolution.
View Article and Find Full Text PDFJ Exp Zool B Mol Dev Evol
November 2014
This is an exciting time to be an evolutionary biologist. Indeed, it is difficult to keep up with all the studies that fall under the broad category of "Evolution" since they span species, traits, and scales of organization. This special issue gives a flavor of exciting new approaches in evolutionary biology, but also emphasizes universal themes.
View Article and Find Full Text PDFSingle-cell-resolved measurements reveal heterogeneous distributions of clathrin-dependent (CD) and -independent (CLIC/GEEC: CG) endocytic activity in Drosophila cell populations. dsRNA-mediated knockdown of core versus peripheral endocytic machinery induces strong changes in the mean, or subtle changes in the shapes of these distributions, respectively. By quantifying these subtle shape changes for 27 single-cell features which report on endocytic activity and cell morphology, we organize 1072 Drosophila genes into a tree-like hierarchy.
View Article and Find Full Text PDFAny single-cell-resolved measurement generates a population distribution of phenotypes, characterized by a mean, a variance, and a shape. Here we show that changes in the shape of a phenotypic distribution can signal perturbations to cellular processes, providing a way to screen for underlying molecular machinery. We analyzed images of a Drosophila S2R+ cell line perturbed by RNA interference, and tracked 27 single-cell features which report on endocytic activity, and cell and nuclear morphology.
View Article and Find Full Text PDFExtant eukaryotic cells have a dynamic traffic network that consists of diverse membrane-bound organelles exchanging matter via vesicles. This endomembrane system arose and diversified during a period characterized by massive expansions of gene families involved in trafficking after the acquisition of a mitochondrial endosymbiont by a prokaryotic host cell >1.8 billion years ago.
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