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PMID: 7909812 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 125 ·No. 3 ·1994-05-00 ·Pages 573-82

Riederer MA, Soldati T, Shapiro AD, Lin J, Pfeffer SR

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.

MeSH Terms
Animals Base Sequence Biological Transport CHO Cells Cell Compartmentation Cricetinae Endocytosis Endosomes/metabolism GTP Phosphohydrolases/physiology Golgi Apparatus/metabolism In Vitro Techniques Lectins, C-Type Lysosomes/metabolism,ultrastructure Mannose Receptor 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
Chemicals
Lectins, C-Type Mannose Receptor Mannose-Binding Lectins Mannosephosphates Oligodeoxyribonucleotides Receptors, Cell Surface Receptors, Cytoplasmic and Nuclear mannose-6-phosphate GTP Phosphohydrolases rab GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Riederer M A
Department of Biochemistry, Stanford University School of Medicine, CA 94305-5307.
Soldati T
Shapiro A D
Lin J
Pfeffer S R
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.125.3.573
Published
1994-05-00
Pages
573-82
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119986
Subset
IM
Grants
NIDDK NIH HHS · DK37332 · United States
External Links
PubMed source DOI: 10.1083/jcb.125.3.573 PMC Full Text View journal details
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