Recent advances have uncovered the general protein apparatus used by all eukaryotes for intracellular transport, including secretion and endocytosis, and for triggered exocytosis of hormones and neurotransmitters. Membranes are shaped into vesicles by cytoplasmic coats which then dissociate upon GTP hydrolysis. Both vesicles and their acceptor membranes carry targeting proteins which interact specifically to initiate docking. A general apparatus then assembles at the docking site and fuses the vesicle with its target.

Mechanisms of intracellular protein transport.

Mechanisms of intracellular protein transport

THE definition of cellular organelles has evolved over the last hundred years largely driven by morphologic observations, but more recently has been supplemented and complemented by functional and biochemical studies (Palade, 1975) . Thus, organelles are now identified both by their morphology and by the set ofcomponents that comprise them . Determining how organelle identity is established and maintained and how newly synthesized protein and membrane are sorted to different organelles are the central issues of organellogenesis . Essential to the many cellular functions that take place within the central vacuolar system (which consists ofthe ER, Golgi apparatus, secretory vesicles, endosomes, and lysosomes) is membrane traffic which mediates the exchange of components between different organelles . There are two critical characteristics of membrane traffic . First, only certain sets oforganelles exchange membrane and the patterns of this exchange define what are called membrane pathways . Second, multiple pathways intersect at specific points within the central vacuolar system . For specific components to "choose" the correct pathway at such points of crossing, mechanisms exist to impose choices on specific molecules . This process is called sorting . The characteristicsofeachorganelle within the central vacuolar system are likely to be intimately tied to the properties ofmembrane traffic . An imbalance in the magnitude ofmembrane input into and egress from an organelle would have profound effects on the size ofthat compartment . In addition, failures in sorting or aberrations in targeting pathways would be expected to profoundly affect the identity of individual organelles . Recently, the relationship between the control of membrane traffic and the maintenance of organelle structure has been investigated with the use ofa remarkable drug, brefeldin A (BFA).' In this review we will summarize recent findings with BFA and propose some speculative models concerning the mechanism and regulation ofmembrane traffic within the central vacuolar system .

/pdf/brefeldin-a-insights-into-the-control-of-membrane-traffic-2e22zfg924.pdf

Brefeldin A: insights into the control of membrane traffic and organelle structure.

COPII: a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum.

Rho family GTPases regulate the cytoskeleton and cell migration and are frequently overexpressed in tumours. Here, we identify two modes of tumour-cell motility in 3D matrices that involve different usage of Rho signalling. Rho signalling through ROCK promotes a rounded bleb-associated mode of motility that does not require pericellular proteolysis. This form of motility requires ezrin, which is localized in the direction of cell movement. In contrast, elongated cell motility is associated with Rac-dependent F-actin-rich protrusions and does not require Rho, ROCK or ezrin function. Combined blockade of extracellular proteases and ROCK negates the ability of tumour cells to switch between modes of motility and synergises to prevent tumour cell invasion.

Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis

β-COP, a 110 kd protein associated with non-clathrin-coated vesicles and the Golgi complex, shows homology to β-adaptin

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β-COP, a 110 kd protein associated with non-clathrin-coated vesicles and the Golgi complex, shows homology to β-adaptin