Vesicle-associated membrane protein

Function

Vesicle-associated membrane protein (VAMP) has been implicated in synaptic vesicle docking and fusion^[1].

VAMP2 is part of the protein complex which in volve Syntaxin and SNAP25 which is involved in the docking or fusion of synaptic vesicles with the presynaptic ^[2].
VAMP4 is involved in the pathway that functions to remove an inhibitor (probably synaptotagmin) of calcium-triggered exocytosis during the maturation of secretory granules.
VAMP8 is involved in the homotypic fusion of secretary granules^[3].

Vesicle-associated membrane protein-associated protein (VAP) are endoplasmic reticulum proteins functioning in vesicle traffic, neurotransmitter release, microtubule organisation, lipid transport and unfolded protein transport^[4].

Relevance

Decreased levels of VAMP2 and α-synuclein correlate with duration of dementia^[5]. Decreased level of VAMPB/C is observed in ALS spinal cord ^[6].

Structural highlights

There is a remarkable shape complementarity between the proteins involved in the SNARE-complexin-synaptotagmin interface^[7].

Rat vesicle-associated membrane protein 2 SNARE motif (grey) complex with syntaxin-1A SNARE motif (green), SNAP25 SNARE motif (pink and yellow), complexin-1 (magenta), synaptotagmin-1 (cyan), glycerol and Mg+2 ion (green) (PDB code 5w5c)

Drag the structure with the mouse to rotate

3D structures of vesicle-associated membrane protein3D structures of vesicle-associated membrane protein

Updated on 18-March-2024

ReferencesReferences

↑ Calakos N, Scheller RH. Vesicle-associated membrane protein and synaptophysin are associated on the synaptic vesicle. J Biol Chem. 1994 Oct 7;269(40):24534-7. PMID:7929121
↑ Behrendorff N, Dolai S, Hong W, Gaisano HY, Thorn P. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) selectively required for sequential granule-to-granule fusion. J Biol Chem. 2011 Aug 26;286(34):29627-34. doi: 10.1074/jbc.M111.265199. Epub, 2011 Jul 6. PMID:21733851 doi:http://dx.doi.org/10.1074/jbc.M111.265199
↑ Behrendorff N, Dolai S, Hong W, Gaisano HY, Thorn P. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) selectively required for sequential granule-to-granule fusion. J Biol Chem. 2011 Aug 26;286(34):29627-34. doi: 10.1074/jbc.M111.265199. Epub, 2011 Jul 6. PMID:21733851 doi:http://dx.doi.org/10.1074/jbc.M111.265199
↑ Lev S, Ben Halevy D, Peretti D, Dahan N. The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol. 2008 Jun;18(6):282-90. PMID:18468439 doi:10.1016/j.tcb.2008.03.006
↑ Vallortigara J, Whitfield D, Quelch W, Alghamdi A, Howlett D, Hortobagyi T, Johnson M, Attems J, O'Brien JT, Thomas A, Ballard CG, Aarsland D, Francis PT. Decreased Levels of VAMP2 and Monomeric Alpha-Synuclein Correlate with Duration of Dementia. J Alzheimers Dis. 2016;50(1):101-10. doi: 10.3233/JAD-150707. PMID:26639969 doi:http://dx.doi.org/10.3233/JAD-150707
↑ Anagnostou G, Akbar MT, Paul P, Angelinetta C, Steiner TJ, de Belleroche J. Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord. Neurobiol Aging. 2010 Jun;31(6):969-85. doi:, 10.1016/j.neurobiolaging.2008.07.005. Epub 2008 Aug 13. PMID:18701194 doi:http://dx.doi.org/10.1016/j.neurobiolaging.2008.07.005
↑ Zhou Q, Zhou P, Wang AL, Wu D, Zhao M, Sudhof TC, Brunger AT. The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis. Nature. 2017 Aug 24;548(7668):420-425. doi: 10.1038/nature23484. Epub 2017 Aug, 16. PMID:28813412 doi:http://dx.doi.org/10.1038/nature23484

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Calakos N, Scheller RH. Vesicle-associated membrane protein and synaptophysin are associated on the synaptic vesicle. J Biol Chem. 1994 Oct 7;269(40):24534-7. PMID:7929121

[2] Behrendorff N, Dolai S, Hong W, Gaisano HY, Thorn P. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) selectively required for sequential granule-to-granule fusion. J Biol Chem. 2011 Aug 26;286(34):29627-34. doi: 10.1074/jbc.M111.265199. Epub, 2011 Jul 6. PMID:21733851 doi:http://dx.doi.org/10.1074/jbc.M111.265199

[3] Behrendorff N, Dolai S, Hong W, Gaisano HY, Thorn P. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) selectively required for sequential granule-to-granule fusion. J Biol Chem. 2011 Aug 26;286(34):29627-34. doi: 10.1074/jbc.M111.265199. Epub, 2011 Jul 6. PMID:21733851 doi:http://dx.doi.org/10.1074/jbc.M111.265199

[4] Lev S, Ben Halevy D, Peretti D, Dahan N. The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol. 2008 Jun;18(6):282-90. PMID:18468439 doi:10.1016/j.tcb.2008.03.006

[5] Vallortigara J, Whitfield D, Quelch W, Alghamdi A, Howlett D, Hortobagyi T, Johnson M, Attems J, O'Brien JT, Thomas A, Ballard CG, Aarsland D, Francis PT. Decreased Levels of VAMP2 and Monomeric Alpha-Synuclein Correlate with Duration of Dementia. J Alzheimers Dis. 2016;50(1):101-10. doi: 10.3233/JAD-150707. PMID:26639969 doi:http://dx.doi.org/10.3233/JAD-150707

[6] Anagnostou G, Akbar MT, Paul P, Angelinetta C, Steiner TJ, de Belleroche J. Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord. Neurobiol Aging. 2010 Jun;31(6):969-85. doi:, 10.1016/j.neurobiolaging.2008.07.005. Epub 2008 Aug 13. PMID:18701194 doi:http://dx.doi.org/10.1016/j.neurobiolaging.2008.07.005

[7] Zhou Q, Zhou P, Wang AL, Wu D, Zhao M, Sudhof TC, Brunger AT. The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis. Nature. 2017 Aug 24;548(7668):420-425. doi: 10.1038/nature23484. Epub 2017 Aug, 16. PMID:28813412 doi:http://dx.doi.org/10.1038/nature23484

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