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CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons.

Hammarlund M, Watanabe S, Schuske K, Jorgensen EM - J. Cell Biol. (2008)

Bottom Line: In Caenorhabditis elegans motor neurons, dense core vesicles dock at the plasma membrane but are excluded from active zones at synapses.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.

ABSTRACT
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.

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Docked dense core vesicles are excluded from active zones. (A and B) Each graph shows the mean number of docked synaptic or dense core vesicles per profile at a given number of sections from the dense projection. Colored bars show the number of profiles required to include 50% of the total number of docked vesicles. Lines show the docked vesicle density in units of vesicles per micrometer. (C) Cumulative probability of vesicle docking relative to distance from the dense projection. The active zone where synaptic vesicles dock is roughly 210 nm in radius (Hammarlund et al., 2007).
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fig3: Docked dense core vesicles are excluded from active zones. (A and B) Each graph shows the mean number of docked synaptic or dense core vesicles per profile at a given number of sections from the dense projection. Colored bars show the number of profiles required to include 50% of the total number of docked vesicles. Lines show the docked vesicle density in units of vesicles per micrometer. (C) Cumulative probability of vesicle docking relative to distance from the dense projection. The active zone where synaptic vesicles dock is roughly 210 nm in radius (Hammarlund et al., 2007).

Mentions: Synaptic vesicles in C. elegans dock to the plasma membrane at the active zone, which flanks the dense projection at synapses (Hammarlund et al., 2007). Similar to the total synaptic vesicle population, half of all docked synaptic vesicles are found in profiles that contain a dense projection (Fig. 3 A, blue bar). This is not simply caused by increased surface area at varicosities; docked synaptic vesicles are more densely packed near the dense projection (Fig. 3 A, blue line). Docked dense core vesicles are more evenly distributed along the axon rather than densely clustered near the dense projection. In fact, profiles with a dense projection are somewhat depleted of docked dense core vesicles (Fig. 3 B, wide bar). Correcting these data for membrane area differences did not affect this trend (Fig. 3 B, red line). To further analyze this apparent depletion, we calculated the distance from the dense projection for each individual docked synaptic and dense core vesicle (Fig. 3 C). Docked dense core vesicles are excluded from the membrane within ∼150 nm of the dense projection, a region that encompasses the active zone. Thus, docking of synaptic and dense core vesicles is partitioned into distinct membrane regions, which suggests that different mechanisms may control these processes.


CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons.

Hammarlund M, Watanabe S, Schuske K, Jorgensen EM - J. Cell Biol. (2008)

Docked dense core vesicles are excluded from active zones. (A and B) Each graph shows the mean number of docked synaptic or dense core vesicles per profile at a given number of sections from the dense projection. Colored bars show the number of profiles required to include 50% of the total number of docked vesicles. Lines show the docked vesicle density in units of vesicles per micrometer. (C) Cumulative probability of vesicle docking relative to distance from the dense projection. The active zone where synaptic vesicles dock is roughly 210 nm in radius (Hammarlund et al., 2007).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2234227&req=5

fig3: Docked dense core vesicles are excluded from active zones. (A and B) Each graph shows the mean number of docked synaptic or dense core vesicles per profile at a given number of sections from the dense projection. Colored bars show the number of profiles required to include 50% of the total number of docked vesicles. Lines show the docked vesicle density in units of vesicles per micrometer. (C) Cumulative probability of vesicle docking relative to distance from the dense projection. The active zone where synaptic vesicles dock is roughly 210 nm in radius (Hammarlund et al., 2007).
Mentions: Synaptic vesicles in C. elegans dock to the plasma membrane at the active zone, which flanks the dense projection at synapses (Hammarlund et al., 2007). Similar to the total synaptic vesicle population, half of all docked synaptic vesicles are found in profiles that contain a dense projection (Fig. 3 A, blue bar). This is not simply caused by increased surface area at varicosities; docked synaptic vesicles are more densely packed near the dense projection (Fig. 3 A, blue line). Docked dense core vesicles are more evenly distributed along the axon rather than densely clustered near the dense projection. In fact, profiles with a dense projection are somewhat depleted of docked dense core vesicles (Fig. 3 B, wide bar). Correcting these data for membrane area differences did not affect this trend (Fig. 3 B, red line). To further analyze this apparent depletion, we calculated the distance from the dense projection for each individual docked synaptic and dense core vesicle (Fig. 3 C). Docked dense core vesicles are excluded from the membrane within ∼150 nm of the dense projection, a region that encompasses the active zone. Thus, docking of synaptic and dense core vesicles is partitioned into distinct membrane regions, which suggests that different mechanisms may control these processes.

Bottom Line: In Caenorhabditis elegans motor neurons, dense core vesicles dock at the plasma membrane but are excluded from active zones at synapses.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus