High impact information on Shank2

• Since this protein represents the first reported natural ligand for the cortactin SH3 domain, we designated it CortBP1 for cortactin-binding protein 1 [1].
• The accumulation of ProSAP1 at synaptic structures was analyzed in the developing cerebral cortex [2].
• Both interaction with the actin-binding protein cortactin and early appearance at postsynaptic sites suggest that ProSAP1/CortBP1 may be involved in the assembly of the PSD during neuronal differentiation [2].
• Homer 1b, a Shank-interacting protein that is linked to group I metabotropic glutamate receptors and IP3 receptors, forms a multiple complex with Shank2 and PLC-beta3 [3].
• In this study, we identified the interaction of PLC-beta3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD) [3].

Biological context of Shank2

• The present study utilized bioinformatics to demonstrate the presence of exons encoding ankyrin repeats in the region preceding the previously described Shank2 gene. cDNA sequencing of mRNA from epithelial cells revealed a novel spliceoform of Shank2, termed Shank2E, that encodes a predicted 200 kDa protein with six N-terminal ankyrin repeats [4].
• The association between SSTR2 and the PDZ-domain of CortBP1 was verified by overlay assays and by coprecipitation after transfection in human embryonic kidney (HEK) cells [5].
• CBP90 was purified from rat brain and its cDNA was cloned from a rat brain cDNA library [6].
• The deduced amino acid sequence of CBP90 had no significant similarity to any other protein, but it had a proline-rich domain at the C-terminal region [6].
• As a result of our ongoing studies on the distribution and function of this novel PDZ domain protein, we now report that the expression of ProSAP1 is restricted neither to neurons and interneuronal junctions nor to the nervous system [7].

Anatomical context of Shank2

• Shank1 and Shank2 transcripts are detectable in the dendritic fields of Purkinje cells, whereas Shank3 mRNA is restricted to cerebellar granule cells [8].
• Characterization of an ankyrin repeat-containing Shank2 isoform (Shank2E) in liver epithelial cells [4].
• ProSAP1/Shank2 was present postsynaptically at the glutamatergic ribbon synapses of photoreceptor and bipolar cells, and it was absent from glycinergic and GABAergic amacrine cell synapses [9].
• The ProSAP/Shank family of multidomain proteins of the postsynaptic density (PSD) can either directly or indirectly interact with NMDA-type and metabotropic glutamate receptors and the actin-based cytoskeleton [10].
• The distribution of Abp1, ProSAP1, and ProSAP2 overlaps within the brain, and all three proteins are part of the PSD and are particularly enriched in cortex and hippocampus [11].

Other interactions of Shank2

• We studied the synaptic targeting of multi-domain proteins of the ProSAP/Shank family thought to serve as master scaffolding molecules of the postsynaptic density [12].
• The double-labeling experiments revealed a high rate of colocalization of ProSAP1/Shank2 with Homer1 and PSD-95, and little colocalization with GRIP [9].
• Importantly, different paradigms of neuronal stimulation induce a redistribution of Abp1 to ProSAP-containing synapses [11].
• Our data suggest that IRSp53 can be recruited to the PSD via its ProSAP/Shank interaction and may contribute to the morphological reorganization of spines and synapses after insulin receptor and/or Cdc42Hs activation [10].

Analytical, diagnostic and therapeutic context of Shank2

• With immunocytochemistry and light and electron microscopy, we examined the cellular, synaptic, and postnatal developmental expression of ProSAP1/Shank2 at the synapses of rat retina [9].
• Northern and Western blot analysis indicated that CortBP1 is expressed predominately in brain tissue [1].
• Confocal microscopy of hippocampal neurons showed that ProSAP1 is predominantly localized in synapses, and immunoelectron microscopy in situ revealed a strong association with PSDs of hippocampal excitatory synapses [2].
• Analysis by confocal microscopy indicates that CortBP1 is distributed diffusely throughout the cytosol in transfected cells and that it becomes concentrated at the plasma membrane when SSTR2 is present [5].
• As shown by in situ hybridization, SSTR2 and cortactin-binding protein are coexpressed in the rat brain [5].

References