Amino acid withdrawal induces the formation of autophagosomes, which results in dozens of these large double-membrane vesicles appearing in the starved cell within 10-15 min, and the initiation of autophagy. This vesicle-mediated response clearly requires an adequate supply of membrane and a tight molecular regulation creating a substantial challenge for the cell in terms of vesicle trafficking...

Beth A Tamburini ([email protected]) Tzu L Phang ([email protected]) Susan P Fosmire ([email protected]) Susan C Trapp ([email protected]) Jill E Slansky ([email protected]) Leslie C Sharkey ([email protected]) Gary R Cutter ([email protected]) Donald Bellgrau ([email protected]) Robert M Gemmill ([email protected]) Lawrence E Hunter (larry.hunter@ucdenv...

The cleavage-furrow tip adjacent to the actomyosin contractile ring is believed to be the predominant site for plasma-membrane insertion through exocyst-tethered vesicles during cytokinesis. Here we found that most secretory vesicles are delivered by myosin-V on linear actin cables in fission yeast cytokinesis. Surprisingly, by tracking individual exocytic and endocytic events, we found that ve...

Ras superfamily GTPase activation and inactivation occur by canonical nucleotide exchange and GTP hydrolysis mechanisms. Despite conservation of active-site residues, the Ras-related Rab GTPase activation pathway differs from Ras and between different Rabs. Analysis of DENND1-Rab35, Rabex-Rab5, TRAPP-Rab1 and DrrA-Rab1 suggests Rabs have the potential for activation by distinct GDP-release path...

The dynamic nature of protein structures provides challenges and opportunities for ligand design. I will first discuss some of the different ways in which protein dynamics can be targeted, giving examples from our experience in the design of inhibitors of thymidylate synthase [1-3]. I will then describe the development of a computational toolbox (TRAPP: TRAnsient Pockets in Proteins) to identif...

"Bone density is an important and little-investigated variable about which we should like to know more" (American Journal of Physical Anthropology, 1954). Here an anthropologist echoed a nutritionist (Nutrition Reviews, 1952) regarding photoelectric densitometer estimates of x-ray opacity expressed as thickness of an aluminium or ivory step-wedge (or bone slabs) exposed on the same film as a li...