Guidance receptor degradation is required for neuronal connectivity in the drosophila nervous system

W. Ryan Williamson, Taehong Yang, Jonathan R. Terman, P. Robin Hiesinger

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Axon pathfinding and synapse formation rely on precise spatiotemporal localization of guidance receptors. However, little is known about the neuron-specific intracellular trafficking mechanisms that underlie the sorting and activity of these receptors. Here we show that loss of the neuron-specific v-ATPase subunit a1 leads to progressive endosomal guidance receptor accumulations after neuronal differentiation. In the embryo and in adult photoreceptors, these accumulations occur after axon pathfinding and synapse formation is complete. In contrast, receptor missorting occurs sufficiently early in neurons of the adult central nervous system to cause connectivity defects. An increase of guidance receptors, but not of membrane proteins without signaling function, causes specific gain-of-function phenotypes. A point mutant that promotes sorting but prevents degradation reveals spatiotemporally specific guidance receptor turnover and accelerates developmental defects in photoreceptors and embryonic motor neurons. Our findings indicate that a neuron-specific endolysosomal degradation mechanism is part of the cell biological machinery that regulates guidance receptor turnover and signaling.

Original languageEnglish (US)
Article numbere1000553
JournalPLoS Biology
Volume8
Issue number12
DOIs
StatePublished - Dec 2010

Fingerprint

Neurology
nervous system
Nervous System
Drosophila
Neurons
Degradation
receptors
degradation
Synapses
neurons
Sorting
synapse
photoreceptors
axons
Motor Neurons
sorting
Defects
Adenosine Triphosphatases
Membrane Proteins
Embryonic Structures

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Guidance receptor degradation is required for neuronal connectivity in the drosophila nervous system. / Ryan Williamson, W.; Yang, Taehong; Terman, Jonathan R.; Robin Hiesinger, P.

In: PLoS Biology, Vol. 8, No. 12, e1000553, 12.2010.

Research output: Contribution to journalArticle

Ryan Williamson, W. ; Yang, Taehong ; Terman, Jonathan R. ; Robin Hiesinger, P. / Guidance receptor degradation is required for neuronal connectivity in the drosophila nervous system. In: PLoS Biology. 2010 ; Vol. 8, No. 12.
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