Reactome | Dopamine synaptic vesicle docking and priming

Dopamine synaptic vesicle docking and priming

Stable Identifier

R-HSA-380574

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, clathrin-sculpted monoamine transport vesicle membrane, plasma membrane

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Dopamine synaptic vesicle docking and priming

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Dopamine loaded synaptic vesicles are docked, inside the synapse in the presynaptic cell, close to the plasma membrane. The docking brings the vesicles in close proximity to the release site to facilitate the release of dopamine. Some of the molecules involved in the docking process are STXBP1 (Munc 18), RAB3A (Rab3), RIMS1 (Rab 3 interacting molecule, RIM), BZRAP1 (RIM-binding protein), UNC13B (Munc13) and alpha-liprins.

STXBP1 is an SM (Sec1/Munc18-like) protein that probably functions by wrapping around the trans-SNARE complex to catalyze membrane fusion. It binds to the amino-terminus of STX1A (syntaxin-1A) (Dulubova et al. 1999) and though it's exact role is unclear (Sudhof & Riso 2011), it is essential for membrane fusion in vivo (Khvotchev et al. 2007).

During synaptic exocytosis synaptic vesicles dock with an electron-dense structure called the presynaptic active zone. This has at least four key protein components: UNC13B, RIMS1, BZRAP1 and alpha-liprins. UNC13B is essential for synaptic priming (Augustin et al. 1999). The amino-terminal zinc-finger domain of RIMS1 interacts with the amino-terminal C2a-domain of UNC13B (Lu et al. 2006). A proline-rich domain in RIMS1 interacts with an SH3 domain in BZRAP1 (Wang et al. 2000). Alpha-liprins bind the C2B domain of RIMS1 (Schoch et al. 2002). RIMS1 binds to synaptic vesicle-bound RAB3A (Lu et al. 2006) and possibly SYT1 (synaptotagmin). RIMS1 and BZRAP1 bind to N and P/Q-type calcium channels in the plasma membrane (Kaeser et al. 2011).

The priming reaction brings docked but unprimed synaptic vesicles into a releasable pool. Priming involes formation of the trimeric SNARE complex between two plasma membrane proteins SNAP25 and Syntaxin and vesicular membrane protein, VAMP2.

Literature References

PubMed ID	Title	Journal	Year
15935055	Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation Toonen, RF, de Vries, KJ, Zalm, R, Südhof, TC, Verhage, M	J Neurochem	2005
9701566	Interaction of Munc-18-2 with syntaxin 3 controls the association of apical SNAREs in epithelial cells Riento, K, Galli, T, Jansson, S, Ehnholm, C, Lehtonen, E, Olkkonen, VM	J Cell Sci	1998
18617632	Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux Binda, F, Dipace, C, Bowton, E, Robertson, SD, Lute, BJ, Fog, JU, Zhang, M, Sen, N, Colbran, RJ, Gnegy, ME, Gether, U, Javitch, JA, Erreger, K, Galli, A	Mol Pharmacol	2008
17989281	Dual modes of Munc18-1/SNARE interactions are coupled by functionally critical binding to syntaxin-1 N terminus Khvotchev, M, Dulubova, I, Sun, J, Dai, H, Rizo, J, Südhof, TC	J Neurosci	2007