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Scientific article
Open access
English

Lysosome biogenesis requires Rab9 function and receptor recycling from endosomes to the trans-Golgi network

Published inThe Journal of cell biology, vol. 125, no. 3, p. 573-582
Publication date1994
Abstract

Newly synthesized lysosomal enzymes bind to mannose 6-phosphate receptors (MPRs) in the TGN, and are carried to prelysosomes, where they are released. MPRs then return to the TGN for another round of transport. Rab9 is a ras-like GTPase which facilitates MPR recycling to the TGN in vitro. We show here that a dominant negative form of rab9, rab9 S21N, strongly inhibited MPR recycling in living cells. The block was specific in that the rates of biosynthetic protein transport, fluid phase endocytosis and receptor-mediated endocytosis were unchanged. Expression of rab9 S21N was accompanied by a decrease in the efficiency of lysosomal enzyme sorting. Cells compensated for the presence of the mutant protein by inducing the synthesis of both soluble and membrane-associated lysosomal enzymes, and by internalizing lysosomal enzymes that were secreted by default. These data show that MPRs are limiting in the secretory pathway of cells expressing rab9 S21N and document the importance of MPR recycling and the rab9 GTPase for efficient lysosomal enzyme delivery.

Keywords
  • Animals
  • Base Sequence
  • Biological Transport
  • CHO Cells
  • Cell Compartmentation
  • Cricetinae
  • Endocytosis
  • Endosomes/metabolism
  • GTP Phosphohydrolases/physiology
  • Golgi Apparatus/metabolism
  • Lectins, C-Type
  • Lysosomes/metabolism/ultrastructure
  • Mannose-Binding Lectins
  • Mannosephosphates/metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides/chemistry
  • Receptors, Cell Surface/metabolism
  • Receptors, Cytoplasmic and Nuclear/metabolism
  • Structure-Activity Relationship
  • rab GTP-Binding Proteins
Affiliation Not a UNIGE publication
Citation (ISO format)
RIEDERER, M A et al. Lysosome biogenesis requires Rab9 function and receptor recycling from endosomes to the trans-Golgi network. In: The Journal of cell biology, 1994, vol. 125, n° 3, p. 573–582. doi: 10.1083/jcb.125.3.573
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0021-9525
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315downloads

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