Showing papers by "Thomas Martin published in 1998"
TL;DR: Common themes of localized signal generation and the spatially localized recruitment of effector proteins appear to underlie mechanisms employed in signal transduction, cytoskeletal, and membrane trafficking events.
Abstract: Signaling roles for phosphoinositides that involve their regulated hydrolysis to generate second messengers have been well characterized. Recent work has revealed additional signaling roles for phosphoinositides that do not involve their hydrolysis. PtdIns 3-P, PtdIns 3,4,5-P3, and PtdIns 4,5-P2 function as site-specific signals on membranes that recruit and/or activate proteins for the assembly of spatially localized functional complexes. A large number of phosphoinositide-binding proteins have been identified as the potential effectors for phosphoinositide signals. Common themes of localized signal generation and the spatially localized recruitment of effector proteins appear to underlie mechanisms employed in signal transduction, cytoskeletal, and membrane trafficking events.
493 citations
TL;DR: CAPS is a functional component of the exocytotic machinery that localizes selectively to DCVs, and it may confer distinct regulatory features on neuropeptide and biogenic amine transmitter secretion.
146 citations
TL;DR: The differential regulation of exocytosis by CAPS, Ca2+, and potential novel cytosolic factor(s) suggests that the docking and fusion machinery controlling DCVs has diverged from that regulating glutamate-containing SVs.
121 citations
TL;DR: CAPS, as a novel neural/endocrine-specific cytosolic and peripheral membrane protein required for the Ca2+-regulated exocytosis of secretory vesicles, may function in regulated exocyTosis as an effector of PtdIns(4,5)P2.
119 citations
TL;DR: Current evidence suggests that NSF functions during an ATP-dependent step after docking but before fusion, and may function to liberate SNARE proteins from complexes so that the proteins on apposed membranes align in a parallel fashion to bring SVs into close contact with the plasma membrane for fusion.
92 citations
TL;DR: Findings suggest Thy-1 is an integral component of many types of regulated secretory vesicles, and plays an important role in the regulated vesicular release of neurotransmitter at the synapse.
Abstract: Thy-1, a glycosylphosphatidylinositol-linked integral membrane protein of the immunoglobulin superfamily, is a component of both large dense-core and small clear vesicles in PC12 cells. A majority of this protein, formerly recognized only on the plasma membrane of neurons, is localized to regulated secretory vesicles. Thy-1 is also present in synaptic vesicles in rat central nervous system. Experiments on permeabilized PC12 cells demonstrate that antibodies against Thy-1 inhibit the regulated release of neurotransmitter; this inhibition appears to be independent of any effect on the Ca2+ channel. These findings suggest Thy-1 is an integral component of many types of regulated secretory vesicles, and plays an important role in the regulated vesicular release of neurotransmitter at the synapse.
55 citations
TL;DR: Several cell-free systems are described for studies of regulated exocytosis derived from PC12 cells, clonal cell lines of adrenal medullary origin, that possess large dense-core vesicles that retain their competence for regulated excytosis in a variety of permeable cell and isolated membrane preparations.
42 citations
TL;DR: In this article, a phospshite/phosphonate exchange reaction was employed for the synthesis of dialkyl esters 5aα-5cα and 5aβ- 5cβ.
33 citations
TL;DR: This chapter describes that dense core vesicles (DCVs) exocytosis in exocrine cells proceeds by mechanisms that are less clearly understood and involves proteins or protein isoforms different from those employed in neural/endocrine secretion.
Abstract: Publisher Summary This chapter describes that dense core vesicles (DCVs) exocytosis in exocrine cells proceeds by mechanisms that are less clearly understood and involves proteins or protein isoforms different from those employed in neural/endocrine secretion. Biochemical and molecular biological studies have resulted in the characterization of at least 25 types of synaptic vesicle (SV) membrane proteins that may mediate aspects of SV function including calcium-dependent exocytosis, endocytosis, and neurotransmitter loading. In neuronal cells, there are important physiological differences between the exocytosis of SVs that contain neurotransmitters such as glutamate and the exocytosis of larger DCVs that contain neuropeptides, including calcium sensitivity and speed. Microinjection and genetic studies have documented the importance of SNARE proteins and synaptotagmin in neurosecretion without revealing their sites of action and mechanisms. Of the other isoforms of synaptotagmin characterized, synaptotagmin III has the most appealing characteristics as a calcium sensor for DCV exocytosis. Expression of synaptotagmin isoforms in the acinar pancreas has not been reported, so it is uncertain whether this protein family plays a role in calcium sensing for zymogen granule exocytosis.
4 citations
1 citations