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J Cell Sci. 2015 Feb 15;128(4):815-27. doi: 10.1242/jcs.166314. Epub 2015 Jan 14.

TOM1 is a PI5P effector involved in the regulation of endosomal maturation.

Author information

1
INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
2
CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse, France Université de Toulouse; UPS; IPBS;, F-31077 Toulouse, France.
3
INSERM U786, Unité de Pathogénie microbienne moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France.
4
INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France CHU de Toulouse, Laboratoire d'Hématologie, 31059 Toulouse Cedex 03, France.
5
INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France helene.tronchere@inserm.fr.

Abstract

Phosphoinositides represent a major class of lipids specifically involved in the organization of signaling cascades, maintenance of the identity of organelles and regulation of multiple intracellular trafficking steps. We previously reported that phosphatidylinositol 5-monophosphate (PI5P), produced by the Shigella flexneri phosphatase IpgD, is implicated in the endosomal sorting of the epidermal growth factor receptor (EGFR). Here, we show that the adaptor protein TOM1 is a new direct binding partner of PI5P. We identify the domain of TOM1 involved in this interaction and characterize the binding motif. Finally, we demonstrate that the recruitment of TOM1 by PI5P on signaling endosomes is responsible for the delay in EGFR degradation and fluid-phase bulk endocytosis. Taken together, our data strongly suggest that PI5P enrichment in signaling endosomes prevents endosomal maturation through the recruitment of TOM1, and point to a new function of PI5P in regulating discrete maturation steps in the endosomal system.

KEYWORDS:

EGFR; Phosphoinositides; Signaling endosome; TOM1; VHS domain

PMID:
25588840
DOI:
10.1242/jcs.166314
[Indexed for MEDLINE]
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