Abstract
In this paper, we report that the PX domain-containing protein SNX16, a member of the sorting nexin family, is associated with late endosome membranes. We find that SNX16 is selectively enriched on tubulo-cisternal elements of this membrane system, whose highly dynamic properties and formation depend on intact microtubules. By contrast, SNX16 was not found on vacuolar elements that typically contain LBPA, and thus presumably correspond to multivesicular endosomes. We conclude that SNX16, together with its partner phosphoinositide, define a highly dynamic subset of late endosomal membranes, supporting the notion that late endosomes are organized in distinct morphological and functional regions. Our data also indicate that SNX16 is involved in tubule formation and cholesterol transport as well as trafficking of the tetraspanin CD81, suggesting that the protein plays a role in the regulation of late endosome membrane dynamics.
Highlights
It is generally accepted that some long-lived lipids are not stochastically distributed in cellular membranes but are differentially distributed in subcellular compartments
We studied the PX domain-containing protein SNX16, which is a member of the sorting nexin family
We find that SNX16, in contrast to other PtdIns(3)P-binding proteins, is not present on early endosomes, yet membrane association depends on an intact PX domain, and is reversed by the PtdIns 3-kinase inhibitor wortmannin
Summary
It is generally accepted that some long-lived lipids are not stochastically distributed in cellular membranes but are differentially distributed in subcellular compartments. Other lipids show restricted distributions, in particular the unconventional phospholipid lysobisphosphatidic acid (LBPA) or bis-monoacylglycerophosphate (BMP), which is abundant in late endosomes and not detected elsewhere in the cell [3]. Phosphoinositides, signaling lipids that are typically very short-lived, are distributed in different cellular territories, through the concerted action of lipid kinases and phosphatases [4,5,6]. PtdIns(4,5)P2 and PtdIns(3,4,5)P3 are present in the plasma membrane, PtdIns(4)P in the Golgi, while PtdIns(3)P and PtdIns(3,5)P2 are both present in endosomes
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