an interaction, receptors would diffuse out of the synapse due to the fluid nature of the lipid membrane. PDZ domains are also utilized to localize elements other than receptor proteins. In the human brain, nitric oxide often acts in the synapse to modify cGMP levels in response to NMDA receptor activation. In order to ensure a favorable spatial arrangements, neuronal nitric oxide synthase (nNOS) is brought close to NMDA receptors via interactions with PDZ domains on PSD-95, which concurrently binds nNOS and NMDA receptors. With nNOS located closely to NMDA receptors, it will be activated immediately after calcium ions begin entering the cell. Regulation PDZ domains are directly involved in the regulation of different cellular pathways. This mechanism of this regulation varies as PDZ domains are able to interact with a range of cellular components. This regulation is usually a result of the co-localization of multiple signaling molecules such as in the example with nNos and NMDA receptors. Some examples of signaling pathway regulation executed by the PDZ domain include phosphatase enzyme activity, mechanosensory signaling, and the sorting pathway of endocytosed receptor proteins. The signaling pathway of the human protein tyrosine phosphatase non-receptor type 4 (PTPN4) is regulated by PDZ domains. This protein is involved in regulating cell death. Normally the PDZ domain of this enzyme is unbound. In this unbound state the enzyme is active and prevents cell signaling for apoptosis. Binding the PDZ domain of this phosphatase results in a loss of enzyme activity, which leads to apoptosis. The normal regulation of this enzyme prevents cells from prematurely going through apoptosis. When the regulation of the PTPN4 enzyme is lost, there is increased oncogenic activity as the cells are able to proliferate. PDZ domains also have a regulatory role in mechanosensory signaling in proprioceptors and vestibular and auditory hair cells. The protein Whirlin (WHRN) localizes in the post-synaptic neurons of hair cells that transform mechanical movement into action potentials that the body can interpret. WHRN proteins contains three PDZ domains. The domains located near the N-terminus bind to receptor proteins and other signaling components. When the one of these PDZ domains is inhibited, the signaling pathways of the neurons are disrupted, resulting in auditory, visual, and vestibular impairment. This regulation is thought to be based on the physical positioning WHRN and the selectivity of its PDZ domain. Regulation of receptor proteins occurs when the PDZ domain on the