TY  - JOUR
AU  - López, David Massa
AU  - Kählau, Lea
AU  - Jungnickel, Katharina Esther Julia
AU  - Loew, Christian
AU  - Damme, Markus
TI  - Characterization of the complex of the lysosomal membrane transporter MFSD1 and its accessory subunit GLMP
JO  - The FASEB journal
VL  - 34
IS  - 11
SN  - 1530-6860
CY  - Hoboken, NJ
PB  - Wiley
M1  - PUBDB-2021-00623
SP  - 14695 - 14709
PY  - 2020
AB  - The two lysosomal integral membrane proteins MFSD1 and GLMP form a tight complex that confers protection of both interaction partners against lysosomal proteolysis. We here refined the molecular interaction of the two proteins and found that the luminal domain of GLMP alone, but not its transmembrane domain or its short cytosolic tail, conveys protection and mediates the interaction with MFSD1. Our data support the finding that the interaction is essential for the stabilization of the complex. These results are complemented by the observation that N‐glycosylation of GLMP in general, but not the type of N‐glycans (high‐mannose‐type or complex‐type) or individual N‐glycan chains, are essential for protection. We observed that the interaction of both proteins already starts in the endoplasmic reticulum, and quantitatively depends on each other. Both proteins can affect vice versa their intracellular trafficking to lysosomes in addition to the protection from proteolysis. Finally, we provide evidence that MFSD1 can form homodimers both in vitro and in vivo. Our data refine the complex interplay between an intimate couple of a lysosomal transporter and its accessory subunit.
LB  - PUB:(DE-HGF)16
C6  - pmid:32959924
UR  - <Go to ISI:>//WOS:000573860500001
DO  - DOI:10.1096/fj.202000912RR
UR  - https://bib-pubdb1.desy.de/record/454621
ER  -