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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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Dense core vesicles do not cluster at active zones. Each graph shows the mean number of synaptic or dense core vesicles per neuronal 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 vesicles. Lines show the vesicle density in units of vesicles per square micrometer.
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fig2: Dense core vesicles do not cluster at active zones. Each graph shows the mean number of synaptic or dense core vesicles per neuronal 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 vesicles. Lines show the vesicle density in units of vesicles per square micrometer.

Mentions: Are dense core vesicles clustered at synapses? The geography of vesicles at the plasma membrane can be described by their proximity to the dense projection, which marks the center of the active zone. Synaptic vesicles are packed tightly around the dense projection (Fig. 2 A), as has been observed previously (Hammarlund et al., 2007). Half of all synaptic vesicles are in profiles containing a dense projection. In contrast, only 26% of dense core vesicles are in such profiles. To encompass 50% of the dense core vesicles near a synapse, it is necessary to extend 140 nm (five profiles) on either side of the dense projection (Fig. 2 B). Furthermore, the density of synaptic vesicles in the cytoplasm is highest in profiles with the dense projection, but the density of dense core vesicles is fairly constant in all sections irrespective of the distance from the neuromuscular junction (Fig. 2, blue and red lines). Thus, dense core vesicles are only slightly enriched at synapses or are evenly distributed along the motor axon and a substantial fraction of dense core vesicles are found quite far from the dense projection.


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)

Dense core vesicles do not cluster at active zones. Each graph shows the mean number of synaptic or dense core vesicles per neuronal 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 vesicles. Lines show the vesicle density in units of vesicles per square micrometer.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Dense core vesicles do not cluster at active zones. Each graph shows the mean number of synaptic or dense core vesicles per neuronal 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 vesicles. Lines show the vesicle density in units of vesicles per square micrometer.
Mentions: Are dense core vesicles clustered at synapses? The geography of vesicles at the plasma membrane can be described by their proximity to the dense projection, which marks the center of the active zone. Synaptic vesicles are packed tightly around the dense projection (Fig. 2 A), as has been observed previously (Hammarlund et al., 2007). Half of all synaptic vesicles are in profiles containing a dense projection. In contrast, only 26% of dense core vesicles are in such profiles. To encompass 50% of the dense core vesicles near a synapse, it is necessary to extend 140 nm (five profiles) on either side of the dense projection (Fig. 2 B). Furthermore, the density of synaptic vesicles in the cytoplasm is highest in profiles with the dense projection, but the density of dense core vesicles is fairly constant in all sections irrespective of the distance from the neuromuscular junction (Fig. 2, blue and red lines). Thus, dense core vesicles are only slightly enriched at synapses or are evenly distributed along the motor axon and a substantial fraction of dense core vesicles are found quite far from the dense projection.

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