A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila.

Anne-Claire Jacomin,Marie-Odile Fauvarque,Emmanuel Taillebourg

doi:10.1186/s12860-016-0115-7

Abstract

BackgroundLysosomes are the major catabolic compartment within eukaryotic cells, and their biogenesis requires the integration of the biosynthetic and endosomal pathways. Endocytosis and autophagy are the primary inputs of the lysosomal degradation pathway. Endocytosis is specifically needed for the degradation of membrane proteins whereas autophagy is responsible for the degradation of cytoplasmic components. We previously identified the deubiquitinating enzyme UBPY/USP8 as being necessary for lysosomal biogenesis and productive autophagy in Drosophila. Because UBPY/USP8 has been widely described for its function in the endosomal system, we hypothesized that disrupting the endosomal pathway itself may affect the biogenesis of the lysosomes.ResultsIn the present study, we blocked the progression of the endosomal pathway at different levels of maturation of the endosomes by expressing in fat body cells either dsRNAs or dominant negative mutants targeting components of the endosomal machinery: Shibire, Rab4, Rab5, Chmp1 and Rab7. We observed that inhibition of endosomal trafficking at different steps in vivo is systematically associated with defects in lysosome biogenesis, resulting in autophagy flux blockade.ConclusionOur results show that the integrity of the endosomal system is required for lysosome biogenesis and productive autophagy in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-016-0115-7) contains supplementary material, which is available to authorized users.

Highlights

Lysosomes are the major catabolic compartment within eukaryotic cells, and their biogenesis requires the integration of the biosynthetic and endosomal pathways
We show that inhibition of endosomal trafficking at different steps is associated with defects in lysosomal biogenesis and blockade of autophagic degradation indicating that a functional endosomal system is required for lysosome biogenesis in vivo
Endosomal trafficking is required for lysosomal biogenesis In order to evaluate the effect of the disruption of the endosomal trafficking on the formation of the lysosome, we affected the function of key players of the endosomal system by expressing Double-stranded RNA (dsRNA) or dominant-negative mutants targeting them

Summary

Introduction

Lysosomes are the major catabolic compartment within eukaryotic cells, and their biogenesis requires the integration of the biosynthetic and endosomal pathways. Lysosomes are the primary degradative organelles of the cell They are found in virtually all eukaryotic cells and were initially described in the 1950s by the Nobel laureate Christian de Duve [1]. Their substrates include all kinds of macromolecules delivered either by endocytosis, phagocytosis or autophagy. The endosomal system constitutes a network of progressively maturing vesicles that is required, among other physiological functions, for the degradation of membrane proteins such as receptors and ionic channels. These proteins enter the endosomal system through clathrin or caveolin-coated vesicles and are delivered to early endosomes. Membrane proteins can either be recycled to the plasma membrane or directed for degradation via the multivesicular bodies (MVB) to late endosomes that eventually fuse with

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