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Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction

Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of s...

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Autores principales: Liao, Edward H., Gray, Lindsay, Tsurudome, Kazuya, El-Mounzer, Wassim, Elazzouzi, Fatima, Baim, Christopher, Farzin, Sarah, Calderon, Mario R., Kauwe, Grant, Haghighi, A. Pejmun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802963/
https://www.ncbi.nlm.nih.gov/pubmed/29373576
http://dx.doi.org/10.1371/journal.pgen.1007184
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author Liao, Edward H.
Gray, Lindsay
Tsurudome, Kazuya
El-Mounzer, Wassim
Elazzouzi, Fatima
Baim, Christopher
Farzin, Sarah
Calderon, Mario R.
Kauwe, Grant
Haghighi, A. Pejmun
author_facet Liao, Edward H.
Gray, Lindsay
Tsurudome, Kazuya
El-Mounzer, Wassim
Elazzouzi, Fatima
Baim, Christopher
Farzin, Sarah
Calderon, Mario R.
Kauwe, Grant
Haghighi, A. Pejmun
author_sort Liao, Edward H.
collection PubMed
description Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons.
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spelling pubmed-58029632018-02-23 Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction Liao, Edward H. Gray, Lindsay Tsurudome, Kazuya El-Mounzer, Wassim Elazzouzi, Fatima Baim, Christopher Farzin, Sarah Calderon, Mario R. Kauwe, Grant Haghighi, A. Pejmun PLoS Genet Research Article Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons. Public Library of Science 2018-01-26 /pmc/articles/PMC5802963/ /pubmed/29373576 http://dx.doi.org/10.1371/journal.pgen.1007184 Text en © 2018 Liao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Liao, Edward H.
Gray, Lindsay
Tsurudome, Kazuya
El-Mounzer, Wassim
Elazzouzi, Fatima
Baim, Christopher
Farzin, Sarah
Calderon, Mario R.
Kauwe, Grant
Haghighi, A. Pejmun
Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction
title Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction
title_full Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction
title_fullStr Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction
title_full_unstemmed Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction
title_short Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction
title_sort kinesin khc-73/kif13b modulates retrograde bmp signaling by influencing endosomal dynamics at the drosophila neuromuscular junction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802963/
https://www.ncbi.nlm.nih.gov/pubmed/29373576
http://dx.doi.org/10.1371/journal.pgen.1007184
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