Sorted JCB Archive

External links to historic papers from JCB. See also the unsorted JCB Archive list.

Membranes

• The invention of freeze fracture EM and the determination of membrane structure Russell Steere introduces his home-made contraption for freeze fracture electron microscopy (EM), and Daniel Branton uses it to conclude that membranes are bilayers.
• Lipid raft idea is floated Gerrit van Meer and Kai Simons get the first hints of lipid rafts based on lipid sorting experiments.
• Spectrin is peripheral S. Jonathan Singer, Garth Nicolson, and Vincent Marchesi use red cell ghosts to provide strong evidence for the existence of peripheral membrane proteins.

Nucleus

• Heterochromatin is late Antonio Lima-de-Faria shows that heterochromatin replicates later than euchromatin.
• The nucleolar origin of rRNA Base compositions and half-lives suggest to Jan-Erik Edström that the nucleolus is the source of rRNA.
• The isolation of the nuclear lamina Aaronson, Blobel, and Gerace define the extent and composition of the nuclear lamina.
• The Hunting of the snRNP Carmo-Fonseca and Lamond track the nuclear travels of snRNPs.
• A portrait of the nuclear pore complex Ron Milligan and Nigel Unwin get a closer look at nuclear pore architecture.
• Chromosome snatching by lateral microtubules Conly Rieder gets kinetochore capture on tape.
• Building a case for the chromosome scaffold William Earnshaw and Margarete Heck localize topo 2 to the base supports of the radial loops of chromatin.
• Centrosome choreography Tony Hyman investigates how centrosome movements are choreographed, and how they determine the division axis.

Ribosomes / endoplasmic reticulum

• Ribosomes, or the particles of Palade George Palade identifies particulate components of the cytoplasm, known initially as the particles of Palade and later as ribosomes.
• Microsomes are the in vitro ER George Palade and Philip Siekevitz unite the fields of microscopy and fractionation in this work. They conclude that Albert Claude’s biochemical fraction called microsomes are the in vitro version of the endoplasmic reticulum (ER) — a cytological feature first noted by Keith Porter.
• Growth cones make proteins, too The recent discovery that elongating axons can synthesize proteins locally is pre-dated by 30 years by Virginia Tennyson’s discovery that growth cones have ribosomes.
• Lost in translation: the signal hypothesis Günter Blobel and Bernhard Dobberstein use a Rube Goldberg concoction of mouse RNA, rabbit ribosomes, and dog ER to reconstruct cell biology's version of the ship in the bottle: how proteins a cell intends to secrete end up in the endoplasmic reticulum.
• Isolating SRP Walter, Blobel, Warren and Dobberstein pin down the proteins (and RNA) that grab onto signal sequences.

Vesicles

• The discovery of synaptic vesicles The visualization of the messengers of the synapse — synaptic vesicles — gives the hypothesis of quantal transmitter release a structural correlate.

Golgi complex

• Sugars sprinkled onto proteins in the Golgi Glycosylation occurs in the Golgi complex, based on labeling with tritiated glucose carried out by Marian Neutra and C.P. Leblond.
• Tagging an organelle Warren, Louvard, and Reggio isolate the first Golgi-specific antibodies.

Exocytosis

• A pathway for secretion Radioactive proteins are followed after their synthesis as they progress towards their secretory fate; this allows the definition of not only trafficking pathways but of the organelles that lie along that pathway.

Lysosmes

• Catching sight of lysosomes Lysosomes are identified by Christian deDuve when a membrane barrier gradually dissolves, thus yielding the tell-tale release of an enzyme activity over time.
• The first supper Fritz Miller and George Palade carry out one of the first examples of combined cytochemistry and electron microscopy. They find that enzymes and substrates colocalize in lysosomes.
• Excess secretory products fuse with lysosomes Robert Smith and Marilyn Farquhar find that excess secretory granules are not stored but fuse with multivesicular bodies (MVBs) that then mature and fuse with lysosomes.
• How to make a lysosome Daniel Friend and Marilyn Farquhar find that transport pathways intersect: synthesized enzyme meets endocytosed protein in the lysosome.

Mitochondria

• There’s DNA in those organelles DNA is directly visualized in first chloroplasts and then mitochondria.
• Were mitochondrial contractions driving the cellular energy cycle? In the days before Mitchell’s chemiosmotic hypothesis, Charles Hackenbrock and others are intrigued by the correlation of an in vitro mitochondrial structural change with oxidative phosphorylation function.

Endocytosis

• Coated pits bring in the yolk A study of yolk protein uptake leads Thomas Roth and Keith Porter to propose that endocytosis is specific to a particular cargo and that the vesicle coat might be functioning in both selection and mechanical molding.
• Curbside recycling at the synapse When John Heuser and Thomas Reese visualize neurotransmitter 'quanta' being released, they also catch sight of endocytic recycling that forms new synaptic vesicles. Ralph Steinman confirms that significant plasma membrane recycling must also be occurring in other cell types.
• Viruses catch an endocytic ride into the cell Ari Helenius puts together snapshots of virus entry to form a coherent sequence of events.

Peroxisomes

• Seeing peroxisomes Christian de Duve’s group isolates and characterizes peroxisomes.

Microtubules

• What the cytoskeleton really looks like Freeze drying gives John Heuser a far more complete view of the cytoskeleton.
• Microtubules get a name Microtubules are named, and recognized as a widespread phenomenon even outside of the spindle.
• Cilia get arms for bending Björn Afzelius identifies cilia arms and comes up with the filament sliding model of cilia movement. The sliding is visualized first by Peter Satir and more directly by Ian Gibbons.
• Microtubules shape the cell Based on cold treatment and correlation, Lewis Tilney and Keith Porter find evidence that microtubule polymerization is important for the development and maintenance of cell shape.
• The discovery of tubulin Tubulin is isolated by Gary Borisy and Edwin Taylor as a colchicine-binding activity, and by Ian Gibbon’s group from cilia.
• Actin and microtubules interact via MAP A viscometer allows Linda Griffith and Tom Pollard to demonstrate that actin and microtubules interact via MAPs.
• Microtubules get dynamicTim Mitchison makes photoactivatable tubulin, allowing him to track flux in the spindle.
• Chromosome snatching by lateral microtubules Conly Rieder gets kinetochore capture on tape.
• Microtubules turn over rapidly Eric Schulze and Marc Kirschner chemically label microtubules to define their dynamics.
• MAP1c is a motor Bryce Paschal and Richard Vallee show that dynein is the other motor.
• Microtubules as a gyroscope for cells on the go Harry Malech, Richard Root, and John Gallin make neutrophils switch their direction, and thus find that microtubules orient and organize the internal structure of migrating cells.

Microfilaments

• What the cytoskeleton really looks like Freeze drying gives John Heuser a far more complete view of the cytoskeleton.
• Not actin, not myosin, but intermediate They are neither thick nor thin: Howard Holtzer identifies intermediate filaments as a completely new kind of filament.
• Actin in non-muscle cells Howard Holtzer’s group uses heavy meromyosin as a probe to find actin filaments in non-muscle cells.
• Actin and microtubules interact via MAP A viscometer allows Linda Griffith and Tom Pollard to demonstrate that actin and microtubules interact via MAPs.
• Actin in locomotion Ken Yamada, Brian Spooner and Norman Wessels use the newly discovered drug cytochalasin B to show that actin filaments drive cell locomotion.
• Actin pushes in bizarre places Lewis Tilney discovers that actin polymerization is a means of force generation. His studies use unorthodox systems: the acrosomal reaction in both starfish and sea cucumber sperm and the cell-to-cell motility of the Listeria monocytogenes bacterium.
• Skeleton crew Anne Ridley and Alan Hall find that rho and its relatives control actin dynamics.
• Powered by gel Thomas Stossel and John Hartwig nab the very first actin-binding protein, find that it spurs actin fibers in vitro to coalesce into a mesh, and tie this process to what happens in vivo during phagocytosis.
• Myosin powers cytokinesis Issei Mabuchi and Makoto Okuno, in the first use of antibodies as protein inhibitors in live cells, show that myosin interacts with actin to provide the force behind cell cleavage.

Adhesion / Cell Junctions

• How vessels become leaky Guido Majno and George Palade find that inflamed blood vessels leak when endothelial cells loosen their grip on one another.
• Defining junctional complexes A mess of nomenclature is sorted out by Marilyn Farquhar and George Palade, who use superb microscopy to define three of the four major types of cell–cell junctions in the polarized epithelial cells of vertebrates.
• Defining gap junctions Jean-Paul Revel and Morris Karnovsky unite the fields of adhesion and intercellular current transfer around a distinct, structural correlate called the gap junction.
• Integrin signal transduction Keith Burridge and Lewis Romer identify FAK as a key relay for passing integrin signals into the cell.
• Sticking it out with tight junctions With persistence and a species change, tight junction proteins are isolated.
• Filling in the gap: cloning a connexin Paul, Goodenough, Kumar and Gilula clone the first connexin proteins.
• Cadherin as a tumor suppressor Behrens and Birchmeier find that cells cut free from their cadherin moorings can metastasize.
• Pursuing the middleman: the hunt for integrins A group of labs use antibodies to find integrins and define their function.
• The sticky business of discovering cadherins A change in the recipe for a trypsin solution allows Masatoshi Takeichi to distinguish calcium-dependent adhesion.

Cell Death

• Autophagy unveiled Autophagy is identified, given a function, and named.
• Hold on for dear life Steve Frisch and Hunter Francis find that epithelial cells that lose touch with the extracellular matrix kill themselves by anoikis.
• Dying On Cue Yuri Lazebnik and William Earnshaw create a system for in vitro apoptosis.
• Active neuronal death Eugene Johnson shows that neurons lacking trophic factors actively kill themselves.

Cell Division

• Tension gets chromosomes oriented Using grasshopper cells in meiosis, Bruce Nicklas and Carol Koch show that attachments of mono-oriented chromosomes can be stabilized using a glass needle to pull on one of the chromosomes. Thus tension between two kinetochores, generated only in the bi-oriented state, might discriminate between correct and incorrect attachments.
• Microtubules park parallel in the half-spindle By defining microtubule polarity in the mitotic spindle, Richard McIntosh narrows down the possible mechanisms used during mitosis.
• An unattached kinetochore screams: “Wait!” Schultz, Rieder and Sluder find that unattached kinetochores tell mitotic cells to wait before dividing.
• Cyclin localization controls activity Jonathon Pines and Tony Hunter show that cyclin activity is controlled by location.
• The kinetochore uncoiled Bill Brinkley and Raymond Zinkowski pull apart the kinetochore.
• Chromosome snatching by lateral microtubules Conly Rieder gets kinetochore capture on tape.
• Myosin powers cytokinesis Issei Mabuchi and Makoto Okuno, in the first use of antibodies as protein inhibitors in live cells, show that myosin interacts with actin to provide the force behind cell cleavage.
• Centrosome choreography Tony Hyman investigates how centrosome movements are choreographed, and how they determine the division axis.

Signaling

• EGF is internalized and degraded Occupied growth factor receptors do not remain statically at the cell surface, say Graham Carpenter and Stanley Cohen, but are internalized to allow continued signaling or downregulation.
• Roll-your-own endothelial tubes Tom Maciag and Michael Stemerman find the critical factor that keeps endothelial cells alive and controls their tube formation.
• Contacting the matrix Can the extracellular matrix (ECM) act as an inducer? Using an ingenious combination of biochemistry and tissue culture on Nucleopore filters, Elizabeth Hay and Stephen Meier show that direct contact with ECM is necessary for corneal epithelium to differentiate.
• In vitro nuclear import In vitro nuclear import assays lead Gerace and Blobel to the importance of the Ran GTPase.
• Pursuing the middleman: the hunt for integrins A group of labs use antibodies to find integrins and define their function.
• BFA sends proteins back Jon Yewdell uses Brefeldin A to detect retrograde trafficking.

Techniques

• Yeast becomes a cell biologist Adams, Pringle, and Kilmartin introduce new antibody techniques, and budding yeast makes its debut as a cell biology workhorse.
• Frog egg extracts can do a cell’s work Manfred Lohka and Yoshio Masui show that frog egg extracts can be used to recreate complex in vivo processes.
• Dishing up bone formation Hiroaki Kodama establishes a cell line of osteoblasts (bone-forming cells) that mineralize in vitro.

Cells

• Endothelial tight junctions form the blood–brain barrier What is the cellular correlate of the so called blood-brain barrier? Thomas Reese and Morris Karnovsky find that it is the junctions between endothelial cells in the brain vasculature. Their discovery comes thanks to three factors: high resolution electron microscopy; the development of sensitive tracer methods; and a fortuitous lunch date.
• A cell line that is under control George Todaro and Howard Green establish the 3T3 cell line — the first well behaved, contact-inhibited cell line.
• A macrophage mystery leads to dendritic discovery In the days before MHC function is defined, digestion of antigens in macrophages is mistakenly taken as evidence against the cells’ role in antigen presentation. But the study leads Ralph Steinman and Zanvil Cohn to their vital discovery of dendritic cells.
• How to spot a satellite cell Based on appearance alone, Alexander Mauro identifies satellite cells as a possible muscle stem cell.

Extracellular Matrix

• ECM determines fate Streuli and Bissell find that extracellular matrix can tell a cell what to do and what to become.
• Basal lamina instructs innervation Joshua Sanes and Jack McMahan show that regenerating nerve axons take their cues for new synapse formation from the extracellular matrix (ECM) of muscle cells and not from the muscle cells themselves.
• ECM signals ECM degradation Damsky and Zena Werb show that changes in ECM interaction change expression of ECM-modifying enzymes.
• More than one way to attach Wen-Tien Chen and S. Jonathan Singer define different connections between membrane receptors and extracellular matrix.
• Making tendons David Birk and Robert Trelstad discover how the cell manipulates collagen to form a tendon.
• Contacting the matrix Can the extracellular matrix (ECM) act as an inducer? Using an ingenious combination of biochemistry and tissue culture on Nucleopore filters, Elizabeth Hay and Stephen Meier show that direct contact with ECM is necessary for corneal epithelium to differentiate.

Yet to be sorted

• 'Porterplasm' and the microtrabecular lattice At the end of a long, distinguished career, Keith Porter tangles with a possible EM artifact.

• A big BiP on the radar screen David Bole and John Kearney track BiP movements and gather evidence for its role as a chaperone.

• Passenger proteins check in Carol Cooke and William Earnshaw identify the first passenger proteins and catalog their strange movements.