Lysosome expansion by selective translation of lysosomal transcripts during phagocyte activation release_ixsw7cz4lfhizpxr4syezl52eu

by Victoria E.B. Hipolito, Jacqueline Diaz, Kristofferson Tandoc, Amra Saric, Ivan Toposiviric, Roberto J Botelho

Released as a post by Cold Spring Harbor Laboratory.

2018  

Abstract

The mechanisms that govern organelle properties to suit the needs of a cell remain poorly defined. Lysosomes degrade cargo from various routes including endocytosis, phagocytosis and autophagy. For phagocytes, lysosomes are a kingpin organelle since they are essential to kill pathogens and process antigens. During phagocyte activation, lysosomes undergo a striking reorganization, changing from dozens of globular structures to a tubular network, in a process that requires the phosphatidylinositol-3-kinase-Akt-mTOR signalling pathway. Here, we show that lysosomes also undergo a rapid expansion in volume and holding capacity during phagocyte activation. Lysosome expansion was paralleled by the induction of lysosomal proteins but this was unexpectedly independent of TFEB and TFE3 transcription factors, known to scale up lysosome biogenesis. Instead, we demonstrate a hitherto unappreciated mechanism of organelle expansion via mTOR-dependent increase in translation of mRNAs encoding key lysosomal proteins including LAMP1 and V-ATPase subunits. Collectively, we identified a mechanism of rapid organelle expansion and remodelling driven by selective enhancement of protein synthesis.
In application/xml+jats format

Archived Files and Locations

application/pdf  6.3 MB
file_jvwiaj6qjvcjxjzelpwf3b5dpq
www.biorxiv.org (repository)
web.archive.org (webarchive)
application/pdf  2.1 MB
file_djxdy4clcrh5dgo3huroc6k26a
www.biorxiv.org (web)
web.archive.org (webarchive)
application/pdf  15.0 MB
file_huxpew6oyffznjvwia35ekkohq
web.archive.org (webarchive)
www.biorxiv.org (web)
Read Archived PDF
Preserved and Accessible
Type  post
Stage   unknown
Date   2018-02-05
Work Entity
access all versions, variants, and formats of this works (eg, pre-prints)
Catalog Record
Revision: bbc08ffb-2267-4fe4-906f-52a74b42dc6f
API URL: JSON