The Insulin Receptor Substrate IRSp53 Links Postsynaptic shank1 to the Small G-Protein cdc42

  title={The Insulin Receptor Substrate IRSp53 Links Postsynaptic shank1 to the Small G-Protein cdc42},
  author={Michaela Soltau and Dietmar Richter and Hans‐J{\"u}rgen Kreienkamp},
  journal={Molecular and Cellular Neuroscience},
The multidomain shank/ProSAP/SSTRIP proteins are major scaffold proteins in glutamatergic synapses in the mammalian brain; expression of shank1/SSTRIP in hippocampal neurons induces morphological changes in dendritic spines, suggesting that shank1 is involved in synapse formation and activity-dependent changes of synaptic structure. Using part of the proline-rich region of shank1 in a yeast two hybrid screen, we identified the insulin receptor substrate IRSp53 as an interaction partner. Overlay… 
Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD‐95
Immunoprecipitation and immunocytochemistry experiments demonstrate that the interaction occurs at postsynaptic sites in the brain and IRSp53 is capable of inducing the formation of a triple complex (shank1/IRSp53/PSD‐95).
The Insulin Receptor Substrate of 53 kDa (IRSp53) Limits Hippocampal Synaptic Plasticity*
The data suggest that the incorporation of IRSp53 into the PSD enables the protein to limit the number of postsynaptic glutamate receptors and thereby affect synaptic plasticity rather than dendritic morphology.
The neuronal proteins CIPP, Cypin and IRSp53 form a tripartite complex mediated by PDZ and SH3 domains
The observation that the three engineered proteins co-localize in the cytoplasm, and at the tip of induced neurites in neuronal cells, raises the interesting possibility that they work together in the formation of neuronal protrusions.
The Shank Family of Postsynaptic Density Proteins Interacts with and Promotes Synaptic Accumulation of the βPIX Guanine Nucleotide Exchange Factor for Rac1 and Cdc42*
A novel interaction between Shank andβPIX, a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases, is reported, suggesting that Shank recruits βPIX and PAK to spines for the regulation of postsynaptic structure.
SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras
SHANKs are established as critical regulators of G-protein signalling and integrin-dependent processes by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane.
Functional analysis of the insulin receptor substrate protein of 53 kDa (IRSp53) in the brain of Mus musculus (Linnaeus 1758)
The postsynaptic density (PSD) of excitatory synapses in the central nervous system (CNS) is a tightly packed compartment that integrates, processes and transmits input signals. A reor-ganisation of
NMDA Receptor-Dependent Synaptic Translocation of Insulin Receptor Substrate p53 via Protein Kinase C Signaling
It is reported here that IRSp53 is accumulated rapidly at the postsynaptic sites of cultured hippocampal neurons after glutamate or NMDA stimulation in an actin cytoskeleton-dependent manner, and this data suggest that IR sp53 is involved in NMDA receptor-linked synaptic plasticity via PKC signaling.
The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells
It is demonstrated that the Shank3 adaptor protein can mediate cellular signaling, and provide a molecular mechanism for the biological divergence between the Ret9 and Ret51 isoform.


The G Protein-coupled Receptor CL1 Interacts Directly with Proteins of the Shank Family*
Shank1 and CL1 are expressed primarily in brain, and both proteins co-enrich in the postsynaptic density, and Shank1 induces a clustering of CL1 in transfected cells, strongly supporting an interaction of both proteins in vivo.
Cdc42hs Facilitates Cytoskeletal Reorganization and Neurite Outgrowth by Localizing the 58-Kd Insulin Receptor Substrate to Filamentous Actin
Results suggest that Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing protein complexes via adaptor proteins such as IRS-58 to F-actin.
The Insulin Receptor Tyrosine Kinase Substrate p58/53 and the Insulin Receptor Are Components of CNS Synapses
It is demonstrated that IRSp58/53 is expressed in the synapse-rich molecular layer of the cerebellum and is highly concentrated at the synapses of cultured hippocampal neurons, where it co-localizes with the insulin receptor.
Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family.
Proteins of the ProSAP family represent a novel link between SAP90/PSD-95 bound membrane receptors and the cytoskeleton at glutamatergic synapses of the central nervous system.
IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling
It is demonstrated that IRSp53, a substrate for insulin receptor with unknown function, is the ‘missing link’ between Rac and WAVE, and is essential for Rac to induce membrane ruffling, which stimulates actin polymerization mediated by the Arp2/3 complex.
Synaptic Scaffolding Proteins in Rat Brain
The data indicate that the Shank1 and -3 family members provide multiple independent connections between synaptic glutamate receptor complexes and the cytoskeleton.
The Calcium-independent Receptor for α-Latrotoxin from Human and Rodent Brains Interacts with Members of the ProSAP/SSTRIP/Shank Family of Multidomain Proteins*
Using yeast two-hybrid screening, a novel interaction between the C termini of CIRL1 and -2 and the PSD-95/discs large/ZO-1 (PDZ) domain of a recently discovered multidomain protein family (ProSAP/SSTRIP/Shank) present in human and rat brain is identified.