Role of Lysosomal Cholesterol in Regulating PI(4,5)P2-Dependent Ion Channel Function.

Abstract

Lysosomes are central regulators of cellular growth and signaling. Once considered the acidic garbage can of the cell, their ever-expanding repertoire of functions include the regulation of cell growth, gene regulation, metabolic signaling, cell migration, and cell death. In this chapter, we detail how another of the lysosome's crucial roles, cholesterol transport, plays a vital role in the control of ion channel function and neuronal excitability through its ability to influence the abundance of the plasma membrane signaling lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This chapter will introduce the biosynthetic pathways of cholesterol and PI(4,5)P2, discuss the molecular mechanisms through which each lipid distinctly regulates ion channels, and consider the interdependence of these lipids in the control of ion channel function.