Essential and selective role of SNX12 in transport of endocytic and retrograde cargo

Priya, Amulya and Sugatha, Jini and Parveen, Sameena and Lacas-Gervais, Sandra and Raj, Prateek and Gilleron, Jerome and Datta, Sunando (2017) Essential and selective role of SNX12 in transport of endocytic and retrograde cargo. In: JOURNAL OF CELL SCIENCE, 130 (16). pp. 2707-2721.

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Abstract

The endosomal protein-sorting machineries play vital roles in diverse physiologically important cellular processes. Much of the core membrane-sorting apparatus is conserved in evolution, such as retromer, which is involved in the recycling of a diverse set of cargoes via the retrograde trafficking route. Here, in an RNAi-based loss-of-function study, we identified that suppression of SNX12 leads to a severe blockage in CIM6PR (also known as IGF2R) transport and alters the morphology of the endocytic compartments. We demonstrate that SNX12 is involved in the early phase of CIM6PR transport, and mediates receptor recycling upstream of the other well-established SNX components of retromer. Ultra-structural analysis revealed that SNX12 resides on tubulo-vesicular structures, despite it lacking a BAR domain. Furthermore, we illustrate that SNX12 plays a key role in intraluminal vesicle formation and in the maturation of a subpopulation of early endosomes into late endosomes, thereby regulating selective endocytic transport of cargo for degradation. This study therefore provides evidence for the existence of early endosomal subpopulations that have differential roles in the sorting of the cargoes along endocytic degradative pathways.

Item Type:	Journal Article
Publication:	JOURNAL OF CELL SCIENCE
Additional Information:	Copy right for this article belongs to the COMPANY OF BIOLOGISTS LTD, BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	01 Sep 2017 06:47
Last Modified:	01 Sep 2017 06:47
URI:	http://eprints.iisc.ac.in/id/eprint/57694

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