Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin

Wahe, Anna, Kasmapour, Bahram, Schmaderer, Christoph, Liebl, David, Sandhoff, Konrad, Nykjaer, Anders, Griffiths, Gareth and Gutierrez, Maximiliano G. (2010) Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin. Journal of Cell Science, 123 14: 2502-2511. doi:10.1242/jcs.067686

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Author Wahe, Anna
Kasmapour, Bahram
Schmaderer, Christoph
Liebl, David
Sandhoff, Konrad
Nykjaer, Anders
Griffiths, Gareth
Gutierrez, Maximiliano G.
Title Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
Publication date 2010-07-15
Sub-type Article (original research)
DOI 10.1242/jcs.067686
Open Access Status File (Publisher version)
Volume 123
Issue 14
Start page 2502
End page 2511
Total pages 10
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Formatted abstract
Sortilin, also known as neurotensin receptor 3 (NTR3), is a transmembrane protein with a dual function. It acts as a receptor for neuromediators and growth factors at the plasma membrane, but it has also been implicated in binding and transport of some lysosomal proteins. However, the role of sortilin during phagosome maturation has not been investigated before. Here, we show that in macrophages, sortilin is mainly localized in the Golgi and transported to latex-bead phagosomes (LBPs). Using live-cell imaging and electron microscopy, we found that sortilin is delivered to LBPs in a manner that depends on its cytoplasmic tail. We also show that sortilin participates in the direct delivery of acid sphingomyelinase (ASM) and prosaposin (PS) to the phagosome, bypassing fusion with lysosomal compartments. Further analysis confirmed that ASM and PS are targeted to the phagosome by sortilin in a Brefeldin-A-sensitive pathway. Analysis of primary macrophages isolated from Sort1−/− mice indicated that the delivery of ASM and PS, but not pro-cathepsin D, to LBPs was severely impaired. We propose a pathway mediated by sortilin by which selected lysosomal proteins are transported to the phagosome along a Golgi-dependent route during the maturation of phagosomes.
Keyword Golgi
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 34 times in Thomson Reuters Web of Science Article | Citations
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