Psychiatry related information on Cttn

• REM sleep deprivation attenuates actin-binding protein cortactin: a link between sleep and hippocampal plasticity [1].

High impact information on Cttn

• Actin and Arf1-dependent recruitment of a cortactin-dynamin complex to the Golgi regulates post-Golgi transport [2].
• Here we show that cortactin associates with the Golgi to regulate the actin- and Dyn2-dependent transport of cargo [2].
• Cortactin is an actin-binding protein that has recently been implicated in endocytosis [2].
• Cortactin antibodies stain the Golgi apparatus, labelling peripheral buds and vesicles that are associated with the cisternae [2].
• Notably, in vitro or intact-cell experiments show that activation of Arf1 mediates the recruitment of actin, cortactin and Dyn2 to Golgi membranes [2].

Biological context of Cttn

• Phosphorylation of cortactin by p21-activated kinase [3].
• Cortactin is an F-actin binding protein that is enriched in dynamic cytoskeletal organelles such as podosomes, membrane ruffles, and lamellipodia [3].
• Transfection of Rat-2 cells with cortactin-specific, RNAi oligonucleotides reduced cortactin protein by 85% and intercellular adhesion by twofold compared with controls (P<0.005) using the donor-acceptor model [4].
• A dynamin-3 spliced variant modulates the actin/cortactin-dependent morphogenesis of dendritic spines [5].
• The lack of REMS, however, severely hampered cortactin protein up-regulation and phosphorylation observed in the PC group suggesting an attenuation of plasticity-related events [1].

Anatomical context of Cttn

• Taken together, these results suggest a role for PAK-phosphorylation of cortactin in the regulation of the dynamics of branched actin filaments in dynamic cytoskeletal organelles [3].
• We have shown previously that Src-phosphorylation of cortactin is not required for its translocation to phorbol-ester induced podosomes in A7r5 aortic smooth muscle cells, but may be important for stability and turnover of podosomes [3].
• Furthermore, selective disruption of the cortactin-Dyn2 interaction significantly reduces the levels of Dyn2 at the Golgi and blocks the transit of nascent proteins from the trans-Golgi network, resulting in swollen and distended cisternae [2].
• Thus, cortactin provides a direct link between the dynamic actin cytoskeleton and the membrane pinchase dynamin that supports vesicle formation during receptor-mediated endocytosis [6].
• These findings suggest that cortactin is an important component of the receptor-mediated endocytic machinery, where, together with actin and dynamin, it regulates the scission of clathrin pits from the plasma membrane [6].

Associations of Cttn with chemical compounds

• Thus cortactin, and phosphorylation of its tyrosine residues, are important for N-cadherin-mediated intercellular adhesion strength [4].
• The Src kinase inhibitor SU-6656 significantly inhibited formation of podosomes induced by phorbol ester and phosphorylation of cortactin, whereas PKCalpha inhibitor did not affect podosome formation in c-Src-transfected cells [7].
• In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization [8].
• Pretreatment of EC with C3 transferase, a specific inhibitor of Rho proteins, significantly inhibited the transmonolayer migration of T lymphocytes, endothelial Rho-GTP loading, and endothelial actin reorganization, without affecting either lymphocyte adhesion to EC or cortactin phosphorylation [9].
• The PC group had more total and tyrosine-phosphorylated cortactin protein expression than the RD and CC groups [1].

Physical interactions of Cttn

• This effect is dependent upon Dyn3 GTPase activity and a direct interaction with the F-actin-binding protein cortactin [5].

Other interactions of Cttn

• While tyrosine phosphorylation of cortactin was not required for recruitment to N-cadherin adhesions it was necessary for cadherin-mediated intercellular adhesion strength [4].
• 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 [10].
• N-syndecan in turn communicates with the cytoskeleton through the cortactin/src-kinase pathway to enhance neurite extension [11].
• Phosphorylation of cortactin and Pyk2/focal adhesion kinase, Src-specific substrates, was increased by Ang II >3-fold, with significantly greater responses in SHR than in WKY (P<0.05) [12].
• Our results suggest that PLC are responsible, via a calcium- and protein kinase C (PKC)-dependent pathway, for p60Src activation and tyrosine phosphorylation of the p60Src substrate, cortactin [13].

Analytical, diagnostic and therapeutic context of Cttn

• Immunoprecipitation and immunoblotting showed that N-cadherin-associated cortactin was phosphorylated on tyrosine residue 421 after intercellular adhesion [4].
• Immunocytochemistry revealed that waves contain a marked concentration of F-actin, GAP-43, cortactin, and ezrin or a related protein, constituents that are also concentrated in growth cones [14].
• The hippocampus was dissected, flash-frozen, and stored for subsequent Western blot or quantitative RT-PCR analysis of cortactin [1].
• Immunofluorescence labeling for actin-binding proteins in immature podocyte showed that alpha-actinin was localized at the level of the junctional complex, whereas cortactin was distributed beneath the entire plasmalemma [15].

References