Endocytosis

CONTENTS 12.1 Introduction .............................................................................................................................. 177 12.2 Caveat Lector ........................................................................................................................... 178 12.3 What Is the Endocytic Pathway? ............................................................................................. 178 12.4 Genes Involved in the Endocytic Vesicle Formation and Internalization Step ....................... 180

12.4.1 Clathrin-Dependent and -Independent Endocytosis ................................................. 180 12.4.2 Endocytosis Appears to be Dynamin Independent ................................................... 181 12.4.3 Adaptors .................................................................................................................... 182

12.5 Accessory Proteins and Scaffolds: Actin Dynamics ............................................................... 183 12.5.1 Las17p Module .......................................................................................................... 183 12.5.2 Abp1p Module .......................................................................................................... 184 12.5.3 Pan1p Module ............................................................................................................ 185

12.6 Membrane Identity Across the Endocytic Pathway ................................................................. 185 12.6.1 Phosphoinositides ...................................................................................................... 185 12.6.2 Rab GTPases ............................................................................................................. 186 12.6.3 Rab5 Domain ............................................................................................................ 187

12.7 SNAREs ................................................................................................................................... 188 12.8 Multivesicular Body Pathway .................................................................................................. 188 12.9 Functional Characterization of Endocytosis in Aspergillus .................................................... 189 12.10 Endocytosis and Signaling ....................................................................................................... 190 References ........................................................................................................................................... 190

12.1 Introduction Endocytosis is the process by which eukaryotic cells take up portions of their plasma membrane with associated proteins and extracellular fl uid. It plays a pivotal role in nutrient acquisition either directly, for example, by mediating the uptake of iron-supplying molecules such as microbial siderophores or mammalian transferrin or, indirectly, by regulating the steady-state at the plasma membrane (i.e., the “expression” at the plasma membrane) of transmembrane domain (TMD)-containing permeases and uptake systems, with one prototypic example in the fungal world being the yeast Gap1p general amino acid permease.1 By mediating the down-regulation of plasma membrane receptors, endocytosis crucially regulates signal transduction, as illustrated by the carcinogenic effect of mutations in metazoan receptor tyrosine kinases that interferes with their ligand-induced internalization and subsequent lysosomal degradation, thus leading to their permanent signaling2-4 or by the antiproliferative effect of mutations impairing the ligand-induced endocytic down-regulation of the G-protein coupled (GPCR) Saccharomyces cerevisiae Ste2p pheromone receptor that results in the inability of mutant yeasts to recover normally from a pheromone-induced cell cycle arrest.5 A further example of involvement of endocytosis in fungal

signal transduction is the essential role of the PalF arrestin in pH.6 When coupled to exocytosis, endocytic recycling creates polarity, as demonstrated with the S. cerevisiae v-SNARE Snc1 in shmoo tips.7 Recycling endosomes ensure delivery of chitin synthase III, a key cell wall biosynthetic enzyme, to polarized sites of growth.8