Abstract

PtdIns(3,5)₂ is involved in a number of cellular processes, such as the regulation of endolysosome morphology and membrane trafficking, autophagy and ion transport. In mammala, PtdIns(3,5)₂ deficiency results in vacuolation most notable in the neurons of the central and peripheral nervous system. This can potentially block the trafficking of neurotransmitters leading to a progression of neurodegeneration diseases such as amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. PtdIns(3,5)₂ is synthesized by the Fab1/PIKfyve lipid kinase and degraded by the Fig4/Sac3 lipid phosphatase. Fab1 and Fig4 are found in a complex with its regulator, the Fac14/ArPIKfyve adaptor protein. The aim of this study was to identify the multimeric state of recombinant Vac14 in order to help elucidate the importance of the Vac14 multimer in the regulation of PtdIns(3,5)₂. The result of this study indicated that recombinant Vac14 forms a homodimer and/or homotrimer.

Highlights

  • 1.1 The eukaryotic cellEukaryotic cells are characterized by a variety of membrane-bound organelles of specialized form and function

  • Fab1 was found to co-localize with FM4-64 on the vacuolar membrane, and mutations on the FYVE domain of the Fab1 kinase resulted in membrane dissociation of Fab1 (Figure 1.5C) [6]. These results suggest that the FYVE domain is responsible for localizing Fab1 to the vacuolar membrane and not the early endosome, as it occurs for other FYVE domain containing proteins like endosome antigen 1 (EEA1)

  • Recent findings indicate the importance of PtdIns(3,5)P2 in various pathways including the regulation of Ca2+ channels, the morphology of late endolysosomal structures, and autophagy [38]

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Summary

Introduction

Eukaryotic cells are characterized by a variety of membrane-bound organelles of specialized form and function. This membrane compartmentalization provides different local environments that segregate specific metabolic functions that are often incompatible with each other, like protein synthesis in the endoplasmic reticulum and protein degradation in lysosomes. Membrane trafficking is a multi-step process that involves the transport of membrane and molecules from one organelle to another [74]. This continuous transport of vesicles is important for the precise control of complex cellular processes such as signal transduction, cell division and cell survival. Understanding the process that regulates membrane trafficking and organelle function is important. 1.2 Membrane trafficking

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