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The lipid phosphatase Sac1 dephosphorylates phosphatidylinositol 4‐phosphate (PI4P), thereby holding levels of this crucial membrane signaling molecule in check. Sac1 regulates multiple cellular processes, including cytoskeletal organization, membrane trafficking and cell signaling. Here, we review the structure and regulation of Sac1, its roles in cell signaling and development and its links to health and disease. Remarkably, many of the diverse roles attributed to Sac1 can be explained by the recent discovery of its requirement at membrane contact sites, where its consumption of PI4P is proposed to drive interorganelle transfer of other cellular lipids, thereby promoting normal lipid homeostasis within cells. [ABSTRACT FROM AUTHOR]

Plant cells contain unique organelles such as chloroplasts with an extensive photosynthetic membrane. In addition, specialized epidermal cells produce an extracellular cuticle composed primarily of lipids, and storage cells accumulate large amounts of storage lipids. As lipid assembly is associated only with discrete membranes or organelles, there is a need for extensive lipid trafficking within plant cells, more so in specialized cells and sometimes also in response to changing environmental conditions such as phosphate deprivation. Because of the complexity of plant lipid metabolism and the inherent recalcitrance of membrane lipid transporters, the mechanisms of lipid transport within plant cells are not yet fully understood. Recently, several new proteins have been implicated in different aspects of plant lipid trafficking. While these proteins provide only first insights into limited aspects of lipid transport phenomena in plant cells, they represent exciting opportunities for further studies. [ABSTRACT FROM AUTHOR]

During neuron development, the biosynthetic needs of the axon initially outweigh those of dendrites. However, although a localized role for the early secretory pathway in dendrite development has been observed, such a role in axon growth remains undefined. We therefore studied the localization of Sar1, a small GTPase that controls ER export, during early stages of neuronal development that are characterized by selective and robust axon growth. At these early stages, Sar1 was selectively targeted to the axon where it gradually concentrated within varicosities in which additional proteins that function in the early secretory pathway were detected. Sar1 targeting to the axon followed axon specification and was dependent on localized actin instability. Changes in Sar1 expression levels at these early development stages modulated axon growth. Specifically, reduced expression of Sar1, which was initially only detectable in the axon, correlated with reduced axon growth, where as overexpression of Sar1 supported the growth of longer axons. In support of the former finding, expression of dominant negative Sar1 inhibited axon growth. Thus, as observed in lower organisms, mammalian cells use temporal and spatial regulation of endoplasmic reticulum exit site (ERES) to address developmental biosynthetic demands. Furthermore, axons, such as dendrites, rely on ERES targeting and assembly for growth. [ABSTRACT FROM AUTHOR]

Compartment-specific control of phosphoinositide lipids is essential for cell function. The Sac1 lipid phosphatase regulates endoplasmic reticulum (ER) and Golgi phosphatidylinositol-4-phosphate [PI(4)P] in response to nutrient levels and cell growth stages. During exponential growth, Sac1p interacts with Dpm1p at the ER but shuttles to the Golgi during starvation. Here, we report that a C-terminal region in Sac1p is required for retention in the perinuclear ER, whereas the N-terminal domain is responsible for Golgi localization. We also show that starvation-induced shuttling of Sac1p to the Golgi depends on the coat protein complex II and the Rer1 adaptor protein. Starvation-induced shuttling of Sac1p to the Golgi specifically eliminates a pool of PI(4)P generated by the lipid kinase Pik1p. In addition, absence of nutrients leads to a rapid dissociation of Pik1p, together with its non-catalytical subunit Frq1p, from Golgi membranes. Reciprocal rounds of association/dissociation of the Sac1p lipid phosphatase and the Pik1p/Frq1p lipid kinase complex are responsible for growth-dependent control of Golgi phosphoinositides. Sac1p and Pik1p/Frq1p are therefore elements of a unique machinery that synchronizes ER and Golgi function in response to different growth conditions. [ABSTRACT FROM AUTHOR]