title: A presynaptic endosomal trafficking pathway controls synaptic growth signaling.
abstract: Structural remodeling of synapses in response to growth signals leads to long-lasting alterations in neuronal function in many systems. Synaptic growth factor receptors alter their signaling properties during transit through the endocytic pathway, but the mechanisms controlling cargo traffic between endocytic compartments remain unclear. Nwk (Nervous Wreck) is a presynaptic F-BAR/SH3 protein that regulates synaptic growth signaling in Drosophila melanogaster. In this paper, we show that Nwk acts through a physical interaction with sorting nexin 16 (SNX16). SNX16 promotes synaptic growth signaling by activated bone morphogenic protein receptors, and live imaging in neurons reveals that SNX16-positive early endosomes undergo transient interactions with Nwk-containing recycling endosomes. We identify an alternative signal termination pathway in the absence of Snx16 that is controlled by endosomal sorting complex required for transport (ESCRT)-mediated internalization of receptors into the endosomal lumen. Our results define a presynaptic trafficking pathway mediated by SNX16, NWK, and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments.
authors.affiliation: Department of Biology, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. arodal@brandeis.edu
authors.forename: Avital A
authors.initials: AA
authors.lastname: Rodal
authors.forename: Aline D
authors.initials: AD
authors.lastname: Blunk
authors.forename: Yulia
authors.initials: Y
authors.lastname: Akbergenova
authors.forename: Ramon A
authors.initials: RA
authors.lastname: Jorquera
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Buhl
authors.forename: J Troy
authors.initials: JT
authors.lastname: Littleton
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015398:Signal Transduction; D058305:Sorting Nexins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D009419:Nerve Tissue Proteins; C558607:SNX16 protein, Drosophila; D058305:Sorting Nexins; C483010:nwk protein, Drosophila