scholarly journals Membrane Association Domains in Ca2+-dependent Activator Protein for Secretion Mediate Plasma Membrane and Dense-core Vesicle Binding Required for Ca2+-dependent Exocytosis

2002 ◽  
Vol 277 (24) ◽  
pp. 22025-22034 ◽  
Author(s):  
Ruslan N. Grishanin ◽  
Vadim A. Klenchin ◽  
Kelly M. Loyet ◽  
Judith A. Kowalchyk ◽  
Kyoungsook Ann ◽  
...  
FEBS Journal ◽  
2011 ◽  
Vol 279 (3) ◽  
pp. 384-394 ◽  
Author(s):  
Tetsushi Sadakata ◽  
Yukiko Sekine ◽  
Megumi Oka ◽  
Makoto Itakura ◽  
Masami Takahashi ◽  
...  

2006 ◽  
Vol 17 (5) ◽  
pp. 2101-2112 ◽  
Author(s):  
Takashi Tsuboi ◽  
Mitsunori Fukuda

Synaptotagmin-like protein 4-a (Slp4-a)/granuphilin-a is specifically localized on dense-core vesicles in certain neuroendocrine cells and negatively controls dense-core vesicle exocytosis through specific interaction with Rab27A. However, the precise molecular mechanism of its inhibitory effect on exocytosis has never been elucidated and is still a matter of controversy. Here we show by deletion and chimeric analyses that the linker domain of Slp4-a interacts with the Munc18-1·syntaxin-1a complex by directly binding to Munc18-1 and that this interaction promotes docking of dense-core vesicles to the plasma membrane in PC12 cells. Despite increasing the number of plasma membrane docked vesicles, expression of Slp4-a strongly inhibited high-KCl–induced dense-core vesicle exocytosis. The inhibitory effect by Slp4-a is absolutely dependent on the linker domain of Slp4-a, because substitution of the linker domain of Slp4-a by that of Slp5 (the closest isoform of Slp4-a that cannot bind the Munc18-1·syntaxin-1a complex) completely abrogated the inhibitory effect. Our findings reveal a novel docking machinery for dense-core vesicle exocytosis: Slp4-a simultaneously interacts with Rab27A and Munc18-1 on the dense-core vesicle and with syntaxin-1a in the plasma membrane.


2008 ◽  
Vol 180 (3) ◽  
pp. 483-491 ◽  
Author(s):  
Marc Hammarlund ◽  
Shigeki Watanabe ◽  
Kim Schuske ◽  
Erik M. Jorgensen

Docking to the plasma membrane prepares vesicles for rapid release. Here, we describe a mechanism for dense core vesicle docking in neurons. In Caenorhabditis elegans motor neurons, dense core vesicles dock at the plasma membrane but are excluded from active zones at synapses. We have found that the calcium-activated protein for secretion (CAPS) protein is required for dense core vesicle docking but not synaptic vesicle docking. In contrast, we see that UNC-13, a docking factor for synaptic vesicles, is not essential for dense core vesicle docking. Both the CAPS and UNC-13 docking pathways converge on syntaxin, a component of the SNARE (soluble N-ethyl-maleimide–sensitive fusion protein attachment receptor) complex. Overexpression of open syntaxin can bypass the requirement for CAPS in dense core vesicle docking. Thus, CAPS likely promotes the open state of syntaxin, which then docks dense core vesicles. CAPS function in dense core vesicle docking parallels UNC-13 in synaptic vesicle docking, which suggests that these related proteins act similarly to promote docking of independent vesicle populations.


2021 ◽  
Vol 2 (1) ◽  
pp. 100325
Author(s):  
Alessandro Moro ◽  
Rein I. Hoogstraaten ◽  
Claudia M. Persoon ◽  
Matthijs Verhage ◽  
Ruud F. Toonen

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