Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation

Viktor I. Korolchuk, Martin M. Schütz, Carolina Gómez-Llorente, João Rocha, Nico R. Lansu, Stephanie M. Collins, Yogesh Wairkar, Iain M. Robinson, Cahir J. O'Kane

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63 Scopus citations

Abstract

TO identify novel proteins required for receptor-mediated endocytosis, we have developed an RNAi-based screening method in Drosophila S2 cells, based on uptake of a scavenger receptor ligand. Some known endocytic proteins are essential for endocytosis in this assay, including clathrin and α-adaptin; however, other proteins important for synaptic vesicle endocytosis are not required. In a small screen for novel endocytic proteins, we identified the Drosophila homologue of Vps35, a component of the retromer complex, involved in endosome-to-Golgi trafficking. Loss of Vps35 inhibits scavenger receptor ligand endocytosis, and causes mislocalisation of a number of receptors and endocytic proteins. Vps35 has tumour suppressor properties because its loss leads to overproliferation of blood cells in larvae. Its loss also causes signalling defects at the neuromuscular junction, including upregulation of TGFβ/BMP signalling and excessive formation of synaptic terminals. Vps35 negatively regulates actin polymerisation, and genetic interactions suggest that some of the endocytic and signalling defects of vps35 mutants are due to this function.

Original languageEnglish (US)
Pages (from-to)4367-4376
Number of pages10
JournalJournal of Cell Science
Volume120
Issue number24
DOIs
StatePublished - Dec 15 2007
Externally publishedYes

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Keywords

  • Haemocytes
  • Neuromuscular junction
  • Rac1
  • Retromer
  • RNAi

ASJC Scopus subject areas

  • Cell Biology

Cite this

Korolchuk, V. I., Schütz, M. M., Gómez-Llorente, C., Rocha, J., Lansu, N. R., Collins, S. M., Wairkar, Y., Robinson, I. M., & O'Kane, C. J. (2007). Drosophila Vps35 function is necessary for normal endocytic trafficking and actin cytoskeleton organisation. Journal of Cell Science, 120(24), 4367-4376. https://doi.org/10.1242/jcs.012336