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Reference: Garner et al. Curr. Opin. Neurobio. 10:321-327 (2000)
The membrane-associated cortical cytoskeleton is thought to provide a scaffold for different classes of proteins involved in SV exo- and endocytosis. CASK, a member of the superfamily of membrane-associated guanylate kinase homologs (MAGUK), contains CaMKII like, SH3, PDZ and guanylate kinase like domains. The first domain binds the Munc18 interacting protein Mint1, while the PDZ domain interacts with the cytoplasmic tails of β-neurexin and syndecan. CASK also associates with Velis, a group of proteins containing a single PDZ domain. More recently, the cytoplasmic tail of N-type Ca2+ channels was shown to interact with both the SH3 domain in CASK and the PDZ domain in Mint1. The assembly of voltage-gated Ca2+ channels and Munc18, a negative regulator SV fusion, into one complex suggests a role of this structure in neurotransmitter release. Several studies have directly implicated the CAZ protein Munc13 in regulating SV fusion with the plasma membrane. Munc13 is thought to antagonize Munc18 and promote the assembly of syntaxin into the SNARE fusion complex. It contains several domains interacting with β-spectrin, syntaxin, phorbol esters (C1) and Ca2+/phospholipids (C2). The CAZ protein Rim comprises zinc finger, PDZ and C2 domains. Its ability to bind rab3A/C in a GTP dependent manner, similar to rabphilin, suggests a function in the translocation of SVs from the proximal to the release ready pool. The largest identified CAZ proteins, Bassoon and Piccolo/Aczonin, may extend several hundred nm in length. Both are structurally related proteins contain 10 PBH domains, a pair of zinc fingers and in the case of Piccolo/Aczonin a PDZ and two C2 domains. Piccolo zinc fingers interact with the prenylated rab3 acceptor protein PRA1 suggesting a role in SV exocytosis. Proline rich sequences (PRS) in both proteins may play a role in dynamically tethering components of the endocytotic machinery near active zones via SH3 domains. Relative distances of Rim, Bassoon and/or Piccolo/Aczonin to the active zonal membrane is not known.
Figure 3. Localization of Bassoon in the CAZ of various types of CNS synapses. (a) Mossy fiber terminal (mf) in the CA3 region of the rat hippocampus. Immunoreactivity is highly concentrated at active zones opposite to PSDs (arrowheads). Scale bar 500 nm. Reproduced with permission from [28]. (b) Immunogold localization of Bassoon in an ultrathin cryosection of a CA1 synapse in the rat hippocampus (pre, presynaptic terminal; post, postsynapse). Scale bar 100 nm. (Courtesy of Karin Richter, Magdeburg; reprinted from the research report 1998/99 of the Leibniz Institute for Neurobiology.) (c) Immunogold localization of Bassoon at a rod photoreceptor ribbon synapse of the rabbit retina. H, postsynaptic processes of horizontal cells. The arrowhead marks the tip, the arrow the acriform density at the base of the ribbon. Scale bar 100 nm. Reproduced with permission from [42].
