Both LRR and PDZ domains are required for correct localization. In our study, one of the three functional mutations was located at the third PDZ domain. Prolines were highly conserved in PDZ1 domain, and were less conserved in PDZ3 and PDZ4 domain. They were not conserved in PDZ2 domain. Two of the three functional mutations were not located in either the LRR or the PDZ domain. They were located close to the C terminal of SCRIB, after the fourth PDZ domain. This is similar to the previously published SCRIB mutation p.R1535Q. Our data, when combined with previously published results, suggested that in addition to the LRR and PDZ domains, other regions of the SCRIB protein, especially the C terminus of SCRIB, may play an important role in human SCRIB subcellular localization. We did not detect any obvious adverse effects of the mutations on the physical interaction of SCRIB with VANGL2. Although one of the conservative mutations was located in the third PDZ domain, which is the direct interaction partner with VANGL2 PDZ binding domain, it did not abolish the interaction between SCRIB and VANGL2. SCRIB has four PDZ domains, and both the second and third PDZ domain strongly interact with VANGL2. Although the p.P1043L mutation may affect the third PZD domain, the second PZD domain still could interact with VANGL2, hence compensating for some third PZD domain variations. Due to the quantitative limitation of western blot assay, there is the possibility that these mutations may partly affect the interaction between SCRIB and VANGL2 which could not be detected by Western blotting. The mammalian retina consists of three layers of neurons specialized for light detection and initial processing of visual signals. Photoreceptors are located in the outer layer, and constitute 70% of retinal cells. These cells, which convert light to a neuronal signal, contain specific cellular structures including apical membrane specializations in the “outer segment�� that capture light photons, ribbon-type AbMole Sibutramine HCl synaptic specializations for transmitting neural signals to interneurons in the inner retinal layers, and a unique nuclear chromatin organization to mediate cell-type-specific gene expression while maximizing the amount of light reaching the outer segments. The vast majority of photoreceptors in most mammalian retinas are rods, which are exquisitely sensitive to low levels of light and mediate night vision. 3�C5% of photoreceptors in mouse and human retinas are cones, which mediate color vision in daylight. Cones can be further classified on the basis of the wavelength sensitivity of the light-capturing visual pigment opsin they contain. To 
establish and maintain their structure and function, each photoreceptor subtype expresses a set of specific genes including the characteristic opsin, under the tight regulation of a network of photoreceptor-specific transcription factors.