Ho_Shannon_Cheuk_Ying.pdf (2.77 MB)
Download file

Characterization of the Regulation and Function of Phosphatidylinositol 3,5-Bisphosphate

Download (2.77 MB)
thesis
posted on 23.05.2021, 16:59 by Shannon Cheuk Ying Ho
PtdIns(3,5)P2 is a low abundance phosphoinositide that is involved in a variety of cellular processes. Most notably, PtdIns(3,5)P2 is known to regulate vacuolar/lysosomal morphology. Deficiency in PtdIns(3,5)P2 results in enlargement of the yeast vacuole and, an extensive vacuolation of the late endocytic compartments in higher eukaryotes (1, 2). In addition, PtdIns(3,5)P2 is also involved in cellular functions including membrane trafficking, autophagy, and vacuolar/lysosomal acidification. However, the current study provided evidence that shows that the vacuole/lysosomes of PtdIns(3,5)P2-deficient cells remain acidic. Hence, PtdIns(3,5)P2 may not have a role in steady-state vacuolar/lysosomal acidification. PtdIns(3,5)P2 is synthesized by the Fab1 lipid kinase and degraded by the antagonistic Fig4 lipid phosphatase. Vac14, an adaptor protein, is known to interact with both Fab1 and Fig4 to form a complex on the vacuolar membrane. This study demonstrated that Vac14 is required to form a homodimer for its interaction with Fig4 and Fab1. In addition, formation of the homodimer is necessary for regulation of PtdIns(3,5)P2. Mutations in human Vac14 and Fig4 has been identified in patients with neurodegenerative diseases, such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth Type 4J (3, 4). This study provides an important stepping stone in characterizing the regulatory mechanism and understanding the function of PtdIns(3,5)P2

History

Language

eng

Degree

Doctor of Philosophy

Program

Molecular Science

Granting Institution

Ryerson University Botelho, Roberto

LAC Thesis Type

Dissertation