A variety of approaches have been utilized to identify and characterize the molecules that mediate vesicular trafficking along the secretory pathway. Two approaches that have been particularly fruitful include the genetic dissection of the yeast secretory pathway and the biochemical characterization of proteins involved in the synaptic vesicle membrane trafficking in the mammalian nerve termina...

The actin cytoskeleton provides scaffolding and physical force to effect fundamental processes such as motility, cytokinesis and vesicle trafficking. The Arp2/3 complex nucleates actin structures and contributes to endocytic vesicle invagination and trafficking away from the plasma membrane. Internalisation and directed recycling of integrins are major driving forces for invasive cell motility ...

The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle traffic...

Glucose entry into muscle cells is precisely regulated by insulin, through recruitment of GLUT4 (glucose transporter-4) to the membrane of muscle and fat cells. Work done over more than two decades has contributed to mapping the insulin signalling and GLUT4 vesicle trafficking events underpinning this response. In spite of this intensive scientific research, there are outstanding questions that...

The functional trafficking steps used by soluble NSF attachment protein receptor (SNARE) proteins have been difficult to establish because of substantial overlap in subcellular localization and because in vitro SNARE-dependent binding and fusion reactions can be promiscuous. Therefore, to functionally identify the site of action of the vesicle-associated membrane protein (VAMP) family of R-SNAR...

The effects of quinoline antimalarials on endocytosis by Plasmodium falciparum was investigated by measuring parasite hemoglobin levels, peroxidase uptake, and transport vesicle content. Mefloquine, quinine, and halofantrine inhibited endocytosis, and chloroquine inhibited vesicle trafficking, while amodiaquine shared both effects. Protease inhibitors moderated hemoglobin perturbations, suggest...

The Ras-superfamily of small G proteins is a family of GTP hydrolases that is regulated by GTP/GDP binding states. One member of the Ras-superfamily, Rab, is involved in the regulation of vesicle trafficking, which is critical to endocytosis, biosynthesis, secretion, cell differentiation and cell growth. The active form of the Rab proteins, which contains GTP, can recruit specific binding partn...

Synaptic transmission is mediated by neurotransmitters that are stored in synaptic vesicles (SV) and released at the active zone (AZ). While recent years major progress has been made unraveling molecular machinery responsible for SV docking, fusion exocytosis, mechanisms governing AZ protein trafficking through axons still remain unclear. Here, we performed stop-flow nerve ligation to examine a...

The synaptotagmin family of vesicle proteins is believed to mediate calcium-dependent regulation of membrane trafficking. Detailed biochemical and in vivo studies of the most characterized isoform, synaptotagmin 1 (syt 1), have provided compelling evidence that it functions as a calcium sensor for fast neurotransmitter release at synapses. However, the function of the remaining isoforms is uncl...