Henne WM~Emr SD, 2015

Pubmed ID 26283797
Title Mdm1/Snx13 is a novel ER-endolysosomal interorganelle tethering protein.
Authors W Mike Henne, Lu Zhu, Zsolt Balogi, Christopher Stefan, Jeffrey A Pleiss, Scott D Emr
Abstract Although endolysosomal trafficking is well defined, how it is regulated and coordinates with cellular metabolism is unclear. To identify genes governing endolysosomal dynamics, we conducted a global fluorescence-based screen to reveal endomembrane effector genes. Screening implicated Phox (PX) domain-containing protein Mdm1 in endomembrane dynamics. Surprisingly, we demonstrate that Mdm1 is a novel interorganelle tethering protein that localizes to endoplasmic reticulum (ER)-vacuole/lysosome membrane contact sites (MCSs). We show that Mdm1 is ER anchored and contacts the vacuole surface in trans via its lipid-binding PX domain. Strikingly, overexpression of Mdm1 induced ER-vacuole hypertethering, underscoring its role as an interorganelle tether. We also show that Mdm1 and its paralogue Ydr179w-a (named Nvj3 in this study) localize to ER-vacuole MCSs independently of established tether Nvj1. Finally, we find that Mdm1 truncations analogous to neurological disease-associated SNX14 alleles fail to tether the ER and vacuole and perturb sphingolipid metabolism. Our work suggests that human Mdm1 homologues may play previously unappreciated roles in interorganelle communication and lipid metabolism.
Citation J. Cell Biol. 2015; 210:541-51


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Papers Phenotype Conditions Collection Tested mutants Data Details
Henne WM~Emr SD, 2015 protein/peptide localization (Mup1) standard [standard] hap a ~4,700 None

Curation history

Dec. 29, 2016 Tested strains to request.
Dec. 29, 2016 Data to request.
May 9, 2017 Tested strains requested.
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May 9, 2017 Data requested.
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