![segital section of thebrain segital section of thebrain](https://media.sciencephoto.com/image/c0056031/800wm/C0056031-Head_and_brain_in_sagittal_section.jpg)
Its optical transparency during early development enables non-invasive monitoring and in vivo analysis of cellular behaviors 21, 22. Zebrafish show conserved physiology and anatomy with mammals 20. Previous studies demonstrated that zebrafish Danio rerio Vsp (Dr-Vsp or Dr-Tpte, hereafter referred to as Dr-Vsp) shares similar molecular architecture to other known Vsp proteins and preserves their key biophysical properties 18, 19. However, the physiological function of Vsp in most organs remains elusive. Our recent study has identified that mouse Vsp is required for normal sperm motility through its role in regulating the spatial distribution of PI(4,5)P 2 in sperm flagellum 11. Vsp expression has been detected in various animal tissues, including testis 10, 11, 12, epithelial cells of digestive tract and renal tubules 13, 14, 15, 16, neurons 6, 17, and blood cells 13. Vsp orthologs are widely conserved across animal species, and their biophysical properties have been intensively investigated using in vitro approach. Among four subreactions, the reaction with PI(4,5)P 2 to produce PI(4)P is the most robust 7, 9. Unlike PTEN, which exhibits rigid 3-phosphatase activity toward PI(3,4,5)P 3 and PI(3,4)P 2, Vsp exhibits activities of both 3- and 5-phosphatases, thereby mediating four subreactions: dephosphorylating PI(3,4,5)P 3 to PI(4,5)P 2 or PI(3,4)P 2 and from PI(4,5)P 2 or PI(3,4)P 2 to PI(4)P 6, 7, 8. Vsp functions upon membrane depolarization to exhibit voltage-dependent phosphatase activity towards PIPs thus, directly translating membrane electrical activities into intracellular PIP signals. Encoded by tpte gene, Vsp is a unique membrane protein with two functional domains: the voltage sensor domain (VSD), as typically found in voltage-gated ion channels and the cytoplasmic catalytic region sharing molecular similarity to the phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor-suppressing PIP phosphatase. Voltage-sensing phosphatase (Vsp, also known as Tpte) is among the key molecules that regulate PIPs’ homeostasis. Because of their essential roles, PIPs have attracted research attention for their regulatory mechanism and fundamental interplay in cell physiology. These interconvertible PIP species are distinctly localized at the plasma membrane and subcellular compartments, regulating specific membrane-associated activities within the cells, including membrane dynamics and cellular trafficking 1, 2, 3, 4, 5. Differential phosphorylation of inositol head groups at the 3-, 4-, and 5-phosphate positions results in seven PIP species: three mono-phosphorylated PIPs, three bi-phosphorylated PIPs, and a single tri-phosphorylated PIP. Phosphoinositides (PIPs) are essential phospholipids that constitute eukaryotic biological membranes. These findings signify a crucial role of Vsp in regulating endocytosis-dependent nutrient absorption in specialized enterocytes across animal species. Furthermore, our comparative study on marine invertebrate Ciona intestinalis Vsp (Ci-Vsp) revealed co-expression with endocytosis-associated genes in absorptive epithelial cells of the Ciona digestive tract, corresponding to zebrafish LREs. Dr-Vsp-deficient zebrafish exhibited growth restriction and higher mortality during the critical period when zebrafish larvae rely primarily on exogenous feeding via intestinal absorption. Dr-Vsp-deficient LREs were remarkably defective in forming endosomal vacuoles after initial uptake of dextran and mCherry. Here we report that zebrafish Vsp (Dr-Vsp), encoded by tpte gene, is functionally expressed on the endomembranes of lysosome-rich enterocytes (LREs) that mediate dietary protein absorption via endocytosis in the zebrafish mid-intestine.
![segital section of thebrain segital section of thebrain](https://www.mindonmap.com/wp-content/uploads/2022/09/thebrain-review.jpg)
In contrast, the physiological role of Vsp in native tissues remains largely unknown. Vsp orthologs from various species have been intensively investigated toward their biophysical properties, primarily using a heterologous expression system. Voltage-sensing phosphatase (Vsp) is a unique membrane protein that translates membrane electrical activities into the changes of phosphoinositide profiles.