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JOURNAL OF CELL BIOLOGY
Volume 222, Issue 4, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202205133
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In this study, Tex2, a lipid transfer protein found on the tubular endoplasmic reticulum, was discovered to be recruited to late endosomes/lysosomes by TMEM55, phosphatases that convert PI(4,5)P-2 to PI5P on LE/lys. The interaction between Tex2 and TMEM55 is regulated by endosome-resident type 2 PI4K activities. Tex2 knockout results in defects in lysosomal trafficking, digestive capacity, and lipid composition of LE/lys membranes. These findings highlight the importance of Tex2 in maintaining lysosomal functions through its presence at TMEM55-dependent ER-LE/lys MCSs.
ER tubules form and maintain membrane contact sites (MCSs) with late endosomes/lysosomes (LE/lys). The molecular composition and cellular functions of these MCSs are poorly understood. Here, we find that Tex2, an SMP domain-containing lipid transfer protein conserved in metazoan and yeast, is a tubular ER protein and is recruited to ER-LE/lys MCSs by TMEM55, phosphatases that convert PI(4,5)P-2 to PI5P on LE/lys. We show that the Tex2-TMEM55 interaction occurs between an N-terminal region of Tex2 and a catalytic motif in the PTase domain of TMEM55. The Tex2-TMEM55 interaction can be regulated by endosome-resident type 2 PI4K activities. Functionally, Tex2 knockout results in defects in lysosomal trafficking, digestive capacity, and lipid composition of LE/lys membranes. Together, our data identify Tex2 as a tubular ER protein that resides at TMEM55-dependent ER-LE/lys MCSs required for lysosomal functions. Du et al. show that Tex2, a potential lipid transporter on the tubular endoplasmic reticulum, is recruited to late endosomes/lysosomes by endosome-resident phosphatidylinositol 4-phosphatases TMEM55 to regulate the lipid compositions, trafficking, and the functions of lysosomes.
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