title: Normal dynactin complex function during synapse growth in Drosophila requires membrane binding by Arfaptin.
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.
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Chang
authors.forename: Tabita
authors.initials: T
authors.lastname: Kreko
authors.forename: Holly
authors.initials: H
authors.lastname: Davison
authors.forename: Tim
authors.initials: T
authors.lastname: Cusmano
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wu
authors.forename: Adrian
authors.initials: A
authors.lastname: Rothenfluh
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Eaton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D000072159:Dynactin Complex; D018507:Gene Expression Regulation, Developmental; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: C579633:Arfip protein, Drosophila; C105393:DCTN1-p150 protein, Drosophila; C000606364:Dctn1 protein, mouse; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins