Cellular homeostasis in the retina requires the lipid phosphatase Sac1.

The complex functions of cellular membranes, and thus overall cell physiology, depend on the distribution of crucial lipid species. Sac1 is an essential, conserved, ER-localized phosphatase whose substrate, phosphatidylinositol 4-phosphate (PI4P), coordinates secretory trafficking and plasma membrane function. PI4P from multiple pools is delivered to Sac1 by oxysterol-binding protein and related proteins in exchange for other lipids and sterols, which places Sac1 at the intersection of multiple lipid distribution pathways. However, much remains unknown about the roles of Sac1 in subcellular homeostasis and organismal development. Using a temperature-sensitive allele (), we show that Sac1 is required for structural integrity of the retinal floor. The β-integrin Myospheroid, which is necessary for basal cell adhesion, is mislocalized in retinas. In addition, the adhesion proteins Roughest and Kirre, which coordinate apical retinal cell patterning at an earlier stage, accumulate within retinal cells due to impaired endo-lysosomal degradation. Moreover, Sac1 is required for ER homeostasis in retinal cells. Together, our data illustrate the importance of Sac1 in regulating multiple aspects of cellular homeostasis during tissue development.