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Review
. 2017:997:135-147.
doi: 10.1007/978-981-10-4567-7_10.

Discovery and Roles of ER-Endolysosomal Contact Sites in Disease

William Mike Henne  1
Affiliations
Review

Discovery and Roles of ER-Endolysosomal Contact Sites in Disease

William Mike Henne. Adv Exp Med Biol. 2017.

Abstract

Inter-organelle membrane contact sites (MCSs) serve as unique microenvironments for the sensing and exchange of cellular metabolites and lipids. Though poorly defined, ER-endolysosomal contact sites are quickly becoming recognized as centers for inter-organelle lipid exchange and metabolic decision-making. Here, we review the discovery and current state of knowledge of ER-endolysosomal MCSs with particular focus on the molecular players that establish and/or utilize these contact sites in metabolism. We also discuss associations of ER-endolysosomal MCS-associated proteins in human disease, as well as the therapeutic promise these contact sites hold in modulating cellular physiology.

Keywords: Endoplasmic reticulum; Endosome; Inter-organelle; Lysosome; Membrane contact site (MCS).

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Figures

Fig. 10.1
Fig. 10.1
Trafficking pathways in human and yeast ER-endolysosomal systems. (a) Receptor-mediated endocytosis of LDL particles (containing sterol-esters) and their trafficking through the endosomal pathway to late endosomes/lysosomes, where cholesterol-esters within LDL particles are degraded into free cholesterol. Free cholesterol must then leave the lysosome lumen in an NPC1-dependent manner and traffic to the plasma membrane (PM) and/or the endoplasmic reticulum (ER). At the ER, the SREBP system senses local cholesterol levels. Low ER cholesterol induces the translocation and proteolytic cleavage of SREBP-2 at the Golgi, producing a soluble transcription factor which enters the nucleus. (b) The ER-endolysosomal system of budding yeast Saccharomyces cerevisiae. The ER is partitioned into distal cortical ER (cER) and nuclear ER (nER), which makes direct contact with the vacuole/lysosome via the nER vacuole junction (NVJ)
Fig. 10.2
Fig. 10.2
Guide to yeast inter-organelle contact sites and their resident proteins
Fig. 10.3
Fig. 10.3
The nER vacuole junction (NVJ) resident proteins and their architectures. The fluorescence micrograph depicts a living yeast with the ER network labeled in red (DsRed-HDEL protein), the vacuole/lysosome in blue (CMAC dye), and endogenous Nvj1 tagged with GFP (Nvj1-GFP)
See this image and copyright information in PMC

References

    1. AhYoung AP, Jiang J, Zhang J, Khoi Dang X, Loo JA, Zhou ZH, Egea PF. Conserved SMP domains of the ERMES complex bind phospholipids and mediate tether assembly. Proc Natl Acad Sci USA. 2015;112:E3179–E3188. - PMC - PubMed
    1. Akizu N, Cantagrel V, Zaki MS, Al-Gazali L, Wang X, Rosti RO, Dikoglu E, Gelot AB, Rosti B, Vaux KK, et al. Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. Nature genetics. 2015;47:528–534. - PMC - PubMed
    1. Bankaitis VA, Johnson LM, Emr SD. Isolation of yeast mutants defective in protein targeting to the vacuole. Proc Natl Acad Sci USA. 1986;83:9075–9079. - PMC - PubMed
    1. Baumann NA, Sullivan DP, Ohvo-Rekilä H, Simonot C, Pottekat A, Klaassen Z, Beh CT, Menon AK. Transport of newly synthesized sterol to the sterol-enriched plasma membrane occurs via nonvesicular equilibration. Biochemistry. 2005;44:5816–5826. - PubMed
    1. Belvedere R, Bizzarro V, Forte G, Dal Piaz F, Parente L, Petrella A. Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway. Sci Rep. 2016;6:29660. - PMC - PubMed

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