Synaptic protein interaction site

The activity of N-type and P/Q-type calcium channels is also regulated by proteins that form part of the synaptic vesicle release machinery (Figure 3). These channel subtypes contain a specific synaptic protein interaction site (termed synprint) in the... 

Harkins AB, Cahill AL, Powers JF, Tischler AS, Fox AP (2004) Deletion of the synaptic protein interaction site of the N-type (CaV2.2) calcium channel inhibits secretion in mouse pheochro-mocytoma cells. Proc Natl Acad Sci U S A 101 15219-24... 

Mochida S, Westenbroek RE, Yokoyama CT, Zhong H, Myers SJ, Scheuer T, Itoh K, CatteraU WA (2003) Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels. Proc Natl Acad Sci U S A 100 2819-24... 

Yokoyama CT, Myers SJ, Fu J, Mockus SM, Scheuer T, Catterall WA (2005) Mechanism of SNARE protein binding and regulation of Cav2 channels by phosphorylation of the synaptic protein interaction site. Mol Cell Neurosci 28 1-17 Yokoyama CT, Sheng ZH, Catterall WA (1997) Phosphorylation of the synaptic protein interaction site on N-type calcium channels inhibits interactions with SNARE proteins. J Neurosci 17 6929-38... 

Fig. 5 GPCR regulation of exocytosis downstream of Ca2+-entry. (a) Sequence of steps leading from recruitment to maturation of synaptic vesicles from a reserve pool (RP) to a readily-releasable pool (RRP) displaying slow (asynchronous) and fast (synchronous highly Ca2+-sensitive pool, HCSP synaptotagmin 1 (SYT 1) supported) components, (b) Protein-protein interactions of SNARES (SYX, syntaxin SYB, synaptobrevin and SNAP-2s-7S complex) and major putative regulatory proteins. Phosphoproteins are shown in shaded boxes (phosphorylation sites for PKA and PKC are indicated where known) with phosphorylation-dependent interactions depicted by arrows (increase indicated by filled arrows decrease indicated by open arrows). Circle-end connectors indicate a phosphorylation-independent or as yet unspecified interaction. Potential effects of interactions at various points of the sequence in A are discussed in the text.

Beaumont V, Zucker RS (2000) Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic Ih channels. Nat Neurosci 3 133 41 Beech DJ, Bernheim L, Hille B (1992) Pertussis toxin and voltage dependence distinguish multiple pathways modulating calcium channels of rat sympathetic neurons. Neuron 8 97-106 Benfenati F, Bahler M, Jahn R et al (1989a) Interactions of synapsin I with small synaptic vesicles distinct sites in synapsin I bind to vesicle phospholipids and vesicle proteins. J Cell Biol 108 1863-72... 

NMDARs are found at both synaptic and extrasynaptic sites, but are present at a much higher density at the synapse. This clustering at the synapse is believed to involve an interaction of the receptor with proteins that are part of the PSD. Identification of the interacting proteins and how these interactions are regulated is central to understanding the trafficking of NMDARs at the synapse. 

Block of this channel in insects by co-agatoxins (14-16) interrupts synaptic transmission by calcium-dependent transmitter release. A third site is a receptor protein for latrotoxins from black widow spider venom ("3" in Figure 1). The latrotoxin receptor appears to be part of a protein scaffold involved in the docking of synaptic vesicles to the inner leaflet of the nerve terminal plasma membrane (17). a-Latrotoxin binding to its receptor leads to massive exocytotic release, presumably due to disruption of vesicle docking protein interactions. It is noteworthy that a-latrotoxin action is vertebrate-speciflc, while a newly described variant of this toxin in the same venom, a-latroinsectotoxin, is highly selective for die insect receptor (4). 

Acetylcholine released by an excited neuron diffuses a few micrometers across the synaptic cleft or neuromuscular junction to the postsynaptic neuron or myocyte, where it interacts with the acetylcholine receptor and triggers electrical excitation (depolarization) of the receiving cell. The acetylcholine receptor is an allosteric protein with two high-affinity binding sites for acetylcholine, about 3.0 nm from the ion gate, on the two a... 

FIGURE 5—70. Substance P and neurokinin 1 receptors, part 3. Shown here is how substance P is formed from gamma PPT-A. Thus, substance P can be formed from three proteins derived from the PPT-A gene, namely, alpha, beta, and gamma PPT-A (see also Figs. 5-68 and 5-69). When substance P is released from neurons, it prefers to interact selectively with the neurokinin 1 subtype of neurokinin receptor (Figs. 5-68 to 5-70). However, there is a mismatch in the brain between the locations of substance P and the NK-1 receptors, suggesting that substance P acts preferentially by volume neurotransmission at sites remote from its axon terminals rather than by classical synaptic neurotransmission. 

---