Normal dynactin complex function during synapse growth in Drosophila requires membrane binding by Arfaptin

Leo Chang, Tabita Kreko, Holly Davison, Tim Cusmano, Yimin Wu, Adrian Rothenfluh, Benjamin A. Eaton

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Mutations in DCTN1, a component of the dynactin complex, are linked to neurodegenerative diseases characterized by a broad collection of neuropathologies. Because of the pleiotropic nature of dynactin complex function within the neuron, defining the causes of neuropathology in DCTN1 mutants has been difficult. We combined a genetic screen with cellular assays of dynactin complex function to identify genes that are critical for dynactin complex function in the nervous system. This approach identified the Drosophila homologue of Arfaptin, a multifunctional protein that has been implicated in membrane trafficking. We find that Arfaptin and the Drosophila DCTN1 homologue, Glued, function in the same pathway during synapse growth but not during axonal transport or synapse stabilization. Arfaptin physically associates with Glued and other dynactin complex components in the nervous system of both flies and mice and colocalizes with Glued at the Golgi in motor neurons. Mechanistically, membrane binding by Arfaptin mediates membrane association of the dynactin complex in motor neurons and is required for normal synapse growth. Arfaptin represents a novel dynactin complex-binding protein that specifies dynactin complex function during synapse growth.

Original languageEnglish (US)
Pages (from-to)1749-1764
Number of pages16
JournalMolecular Biology of the Cell
Volume24
Issue number11
DOIs
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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