| First Author | Jung ES | Year | 2014 |
| Journal | J Physiol | Volume | 592 |
| Issue | 8 | Pages | 1809-21 |
| PubMed ID | 24445315 | Mgi Jnum | J:220651 |
| Mgi Id | MGI:5635776 | Doi | 10.1113/jphysiol.2013.268631 |
| Citation | Jung ES, et al. (2014) Shank2 mutant mice display a hypersecretory response to cholera toxin. J Physiol 592(Pt 8):1809-21 |
| abstractText | Shank2 is a PDZ (PSD-95/discs large/ZO-1)-based adaptor that has been suggested to regulate membrane transporting proteins in the brain and epithelial tissues. Here, we report that Shank2 mutant (Shank2(-/-)) mice exhibit aberrant fluid and ion transport in the intestine. Molecular characterization using epithelial tissues from Shank2(+/+) and Shank2(-/-) mice revealed that a long spliceoform of Shank2 (Shank2E) is predominantly expressed in the pancreatic, renal and intestinal epithelia. In functional assays, deletion of Shank2 increased the cystic fibrosis transmembrane conductance regulator (CFTR)-dependent short-circuit currents by 84% (P < 0.05) and 101% (P < 0.05) in the mouse colon and rectum, respectively. Disruption of the CFTR-Shank2-phosphodiesterase 4D protein complex appeared to be mostly responsible for the changes in CFTR activities. Notably, Shank2 deletion profoundly increased cholera toxin-induced fluid accumulation in the mouse intestine ( approximately 90%, P < 0.01). Analyses with chemical inhibitors confirmed that the hyperactivation of CFTR channel function is responsible for the increased response to cholera toxin. These results suggest that Shank2 is a key molecule that participates in epithelial homeostasis, in particular to prevent overt secretory responses caused by epithelial pathogens. |
