Journal Article

DKFZ-2022-02128

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins.

Pechincha, C. (First author)DKFZ* ; Groessl, S.DKFZ* ; Kalis, R. ; de Almeida, M. ; Zanotti, A. ; Wittmann, M.DKFZ* ; Schneider, M.DKFZ* ; de Campos, R. P.DKFZ* ; Rieser, S. ; Brandstetter, M. ; Schleiffer, A. ; Müller-Decker, K.DKFZ* ; Helm, D.DKFZ* ; Jabs, S. ; Haselbach, D. ; Lemberg, M. K. ; Zuber, J. ; Palm, W. (Last author)DKFZ*

2022
Moses King Cambridge, Mass.

This record in other databases:  

Please use a persistent id in citations: doi:10.1126/science.abn5637

Abstract: Mammalian cells can generate amino acids through macropinocytosis and lysosomal breakdown of extracellular proteins, which is exploited by cancer cells to grow in nutrient-poor tumors. Here, through genetic screens in defined nutrient conditions we characterized LYSET, a transmembrane protein (TMEM251) selectively required when cells consume extracellular proteins. LYSET was found to associate in the Golgi with GlcNAc-1-phosphotransferase, which targets catabolic enzymes to lysosomes through mannose-6-phosphate modification. Without LYSET, GlcNAc-1-phosphotransferase was unstable owing to a hydrophilic transmembrane domain. Consequently, LYSET-deficient cells were depleted of lysosomal enzymes and impaired in turnover of macropinocytic and autophagic cargoes. Thus, LYSET represents a core component of the lysosomal enzyme trafficking pathway, underlies the pathomechanism for hereditary lysosomal storage disorders, and may represent a target to suppress metabolic adaptations in cancer.

Note: #EA:A330#LA:A330# / 2022 Oct 7;378(6615):eabn5637

---

Contributing Institute(s):

1. A330 NWG Signaltransduktion und Stoffwechsel der Zelle (A330)
2. Proteinanalyse (W120)
3. Gruppe Müller-Decker (W420)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---